Chapter 16 Bio

determination

(before scientists figured out what it was it was referred to as this term) unseen events that lead to the observable differentiation of a cell, once a cell has gone through determination an embryonic cell is irreversibly committed to its final fate; even if that cell is experimentally placed in another location in the embryo it will still differentiate into the cell type that is its normal fate (soon as we make the mRNA they will produce proteins and those proteins will have an action)

two major potential uses for human iPS cells

1. cells from patients suffering from diseases can be reprogrammed to become iPS cells which can act as model cells for studying the disease and potential treatments; human iPS cell lines have already been developed from individuals with type 1 diabetes, Parkinsons disease, and at least a dozen other diseases, 2. in the field of regenerative medicine a patients own cells could be reproragmmed into iPS cells and then used to replace nonfunctional tissues, developing techniques that direct iPS cells to become specific cell types for this purpose is an area of intense research and one that has already seen some sucess

downside of cloning

1. in most nucelar translation studies only a small percentage of cloned embryos develop nirmally to birth, 2. like dolly many animals exhibit defects (ex: cloned mice are prone to obesity, pneumonia, liver failure, and premature death), 3. even cloned animals that do appear normally have subtle degects

Normal cell cycle inhibiting pathway p53

1. in the normal pathway DNA damage is an intracellular signal that is passed via protein kinases and leads to activation of p53, 2. activated p53 promotes transcription of the gene for a protein that inhibits the cell cycle (until damaged is repaired), 3. the resulting suppression of cell division ensures that the damaged DNA is not replicated or else it could lead to tumor formation by causing mutations or chromosomal abnormalities, 3. if the damaged DNA is irreparable the p53 signal leafs to programmed cell death/apoptosis results: damaged DNA is not replicated and no cell division

two sources of information tell a cell which genes to express at any given time during embryonic developement

1. one source of imformation in development is the eggs cytoplasm, it contains both RNA and proteins encoded by the mothers DNA and is unevenly spread out; after fetilizaion early mitotic division distribute the zygotes cytoplasm into separate cells (ex: more mitochondria in one cell vs the other, the nuclei of the cells may thus be exposed to different cytoplasmic determinants depending on which portion of the zygotic cytoplasm a cell received, the combination of cytoplasmic determinants in a cell help determine its developmemntal fate by regulating expression of the cells genes during the course of cell differentiation (different proteins within the cell aren't evenly distributed and those proteins have influence on gene espressiona/ different proteins inside the cell to induce transduction pathway to occur and cellular development), it will have a different pathway were certain materials will be turned on or off; different cytoplasmic determinants express different genes (the resulting cells contain different cytoplasmic determinants, which lead to different gene expression), 2. (external) environment around a particular cell (becomes important escpecially as the embryonic cells increases); signals communicated to an embryonic cell from other embroyonic cells in the vicinity is most infleuntial on the growing embryo (types of signals to occur is contact with cell surface molecules on neighboring cells and binding of growth factors secrteded by neighboring cells); such signals causes changes in the target cells (induction); in general these differentated cells will send a signaling molecule to undifferentiated cells and these signals send a cell down a particular path by causing changes in its gene expression (like turns into this or we need you to do this) that results in observable cellular change; interactions between embryonic cells help induce differentiation of the many speciilzized cell types making up a new organism

drisphilia egg develops

1. the egg develops in female overy surrounded by overran cells called nurse cells and follicle cells; these support cells supply the egg with nutrients, mRNA, and other substances needed for development and they also make the egg shape, 2. the nurse cells shrink as they supply nutrients and mRNAs to the developing egg which grows larger, eventually the mature egg fills the Jeff shrill that is secreted by the follicle cells, 3. the egg is fertilized within the mother and then laid, 4. segmented embryo: embryonic development forms (based on where the nurse cells are depleted the head forms), 5. a larva which goes through three stages and the third stage forms a cocoon within which the larva metaphorpheses into the adult

normal cell cycle stumlating pathway for ras

1. the normal pathway is triggered by a growth factor that binds to its receptor in the plasma membrane, 2. the signal is relayed to a G protein called Ras; like all G proteins Ras is active when GTP is bound to it (so GTP is bound to it), 3. Ras [asses the signal to a series of protein kinases, the last kinase activates a transcription factor (activator) that turns on one or more genes for a protein that stimulates the cell cycle

colorectal cancer

140,000 new cases of colorectal cancer are diagnosed each year in the US and disease causes 50,000 deaths each year, it develops gradually, the tumor grows and may become malignant invading other tissues

adenomatous polyposis coli

APC, has multiple functons in the cell including regulation of cell migration and adhesion, 60 percent of colorectal cancer patients have mutated APC (but must occur in both APC alleles), are common in individuals with colorectal cancer

totipotent

Cells that can give rise to all the specialized cell types in the organism are called totipotent (and they can dediffereiate and then give rise to all of them)

gene regulation in cancer

DNA methylation and histone modification patterns differ in normal and cancer cells, miRNAs probably participate in cancer development

pluripotent

ES cells hold more promise than adult stem cells for most medical applications because ES cells are pluripotent which means they are capable of differentiating into many different cell types

Embryonic stem cells

ES, early human embryo at blastocyst stage can generate all embryonic cell types, reproduce indefinitly and depending on culture conditions they can be made to differentiate into a wide variety of specialized cells including even eggs and sperm

inheriting mutations

Individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes (ex: 15 percent of colorectal cancer involve inherited mutations)

BRCA1 and BRCA2

Mutations in the BRCA1 or BRCA2 gene are found in at least half of inherited breast cancers and tests using DNA sequencing can detect these mutations; a women who inherits one mutant BRCA1 allele has 60 percent probabillity of developing breast cancer before the age of 50 compared with only a 2 percent probability for an individual homozygous for the normal allele (ex: skin cells can't be inherited because your not passing on your skin cells to your children the only cancer to be inherited must be found in sperm and egg cells), both BRCA are considered tumor suppressor genes because their wild types alleles protect against breast cancer and their mutant alleles are recessive; there proteins both function in the cells DNA damage repair pathway

reproductive cloning

Reproductive cloning involves creating an animal that is genetically identical to a donor animal through somatic cell nuclear transfer

The bicoid research is important for three reasons

The bicoid research is important for three reasons 1. It identified a specific protein required for some early steps in pattern formation 2. It increased understanding of the mother's role in embryo development 3. It demonstrated a key developmental principle that a gradient of molecules can determine polarity and position in the embryo

kk

The current interest in organismal cloning arises mainly from its potential to generate stem cells

egg polarity genes

These maternal effect genes are also called egg-polarity genes because they control orientation of the egg and consequently the fly; one group of these genes set up the anterior posterior axis of the embryo while a second group establishes the dorsal ventral axis

why was Christiane and Erics goal haunting

They created mutants, conducted breeding experiments, and looked for the corresponding genes 1. there is a sheer number of fruit fly protein coding genes; these genes affecting segmentation might just be a few needles in a hay stack or might be so numerous and varied that the scientists wouldn't be able to make sense of it, 2. mutations affecting a provess as fundamental as segmentation would surely be embryonic lethals; they can never reproduce so they can't be bred for study; do the resarches dealt with this problem by looking for recessive mutations which can be propagated in heterozygotes flies that act as genetic carriers, 3. cytoplasmic determinants in the egg were known to play a role in axis formation so the researchers knew they would have to study the mothers genes as well as those of the embryo; the mothers genes will affect the anterior posteerior body axis and is set up in the developing egg

death

While most cells are differentiating in a developing organism some are genetically programmed to die

regulation during differenation

a bunch of steps in gene expression may be regulated during this step; transcription being the regulatory point

N W and Lewis

a coherent picture of Drophila development emerged (won nobel prize)

in the embryonic develepoment of multicellular organisms

a fertilized egg gives rise to cells of many different types; each with a different structure and corresponding function

Roslin Instutite in Scottland (DOLY)

a lamb cloned from an adult sheep by nuclear transplantation from a differentiated cell, to do this they were able to achieve the necessary dedifferentiation of donor nuclei by cluttering mammary cells in nutrient poor medium; thus stoping the cell cycle, then they fussed these cells with enucleated sheep eggs, then it grew in culture this resulting in diploid cells divided to form early embryos then which were implanted into surrogate mothers (out of several hundred embryos in successfully completed normal development: DOllY)

stem cells

a powerful cell type that is key to the developmental process, they offer hope for medical treatments

how stem cells maintain their own population and generate differentiated cells

a stem cell can divide into another stem cell and a precursor cell (or into two stem cells or two precursor cells), a precursor cell can differentiate into one of several types of cells depending on external factors; thus stem cells can both replensish their own undifferentiated population and generate cells that travel down specific differentiation pathways

how much stem cells do animals have

a very small amount

adult vs embryonic stem cells

adult are harder to grow and give rise to limited number of cell types

adult stem cells

adult body stem cells serve to replace non reproducing specialized cells as needed, adult stem cells are not able to give rise to all cell types in organism though in may cases they can generate multiple types (ex: one of the several types of stem cells in bone marrow can generate all the different kinds of blood cells and another can differentiate into bone, cartilage, fat, muscle, and the linings of blood vessels)

mutations of tumor suppressor genes

any mutations that decreases the normal activity of a tumor suppressor protein may contribute to the onset of cancer in effect stimulating growth through the absent of suppression

proto-oncogenes and tumor suppressor genes

are components of cell signaling pathways

mutations in maternal effect genes

are embryonic lethal (just like segmentation genes)

tissue specific proteins

are found in only a specific cell type and give the cell its characteristic structure and funcion

cells developmental history

begins at the first mitotic division of the zygote (this earliest change that sits a cell on a path to specialization is subtly and only shows up at molecular level), it is how the tissues and organs develops and there cells differentiate and become noticably different in structure and function is the cells developmental history

Edward B Lewis

biologists who showed the value of the genetic approach to studying embryonic development in Drosophila; he studied bizarre mutant flies wit developmental defects that led to extra wings or legs in the wrong places, 1. he first located the mutations on the flys genetic map thus connecting the developmental abnormalities to specific genes; this research supplied the first concrete evidence that genes somehow direct the developmental processes studied by embryologitsts, Lewis discovered the homeotic genes, which control pattern formation in late embryo, larva, and adult stages

where else is stem cells found

brain, skin, hair, eyes, dental pulp, bone marrow, and embryo

tumor viruses

can cause cancer in various animals just like how mutations and other genetic alterations do, viruses play a role in about 15% of human cancers; they do this by interfering with gene regulation in several ways if they integrate their genetic material into the DNA of a cell: viral integration may donate an oncogene to the cell, disrupt a tumor suppressor gene, or convert a proto-oncogene to an oncogene, some viruses produce proteins that inactivate p53 and other tumor suppressor proteins making the cell more prone to becoming cancerous (a virus that caused cancer in chickens called the Epstein Barr virus has been linked to the several types of cancer in humans)

DNA breakage

can contribute to cancer; DNA breakage can contribute to cancer, thus the risk of cancer can be lowered by minimizing exposure to agents that damage DNA such as ultraviolet radiation in sunlight and chemicals found in cigarette smoke; the reason is these things damage DNA and if damages the DNA and we don't catch it (don't have the right proteins to stop it) then we can't fix it and cause mutations

differentiated cells from animals

can't divide in culture and can't develop into the multiple types of a new organism

oncogenes

cancer causing genes (Cancer research led to the discovery of cancer-causing genes called oncogenes in certain types of viruses)

Translocation or transposition

cancer cells are frequently found to contain chromosomes that have broken and rejoined incorrectly translocating fragments from one chromosome to another, consequences of translocation: if a translocated photo-oncogene ends up near an especially active promoter or another control element its transcription may increase making it an oncogene; gene moved to new locus; under new controls (falls under a different activator and promoter thus allowing for the making of a protein)

animal embryos contain stem cells

capable of giving rise to differentiated embryonic cells of any type (anything possible)

zygote to organism three interrelated process of transformations (The transformation from zygote to adult)/ process during embryonic development

cell division, cell differentiation, and morphogenesis (frog to tadpole); all three processes have their basis in cellular behavior; even morphogensis which is the shaping of an organism can be traced back to changes in motility shape and other characteristics of the cells that make up various regions of the embryo

process of apoptosis

cellular agents chop up the DNA and fragment the organelles and other cytoplasmic components, then the cell becomes multilobed which is a change called blebbing and the cells parts are packaged up in vesicles (the cell is shrinking and forming lobes/blebs which are eventually shed as membrane enclosed fragments), these blebs are then engulfed by scavenger cells leaving no trace, apoptosis protets neighboring cells from da,age that they would otherwise suffer if a dying cell mere;y leaked out all its continents including major digestive enzymes

what establishes the axes of the urophilia body?

cytoplasmic determinants in the eggs; these substances are encoded by genes of the mother fittingly called the maternal effect genes

gradients of specific proteins encoded by maternal mRNA

determine the posterior and anterior ends and establish the dorsal ventral axis

opposites during paw development of a mous

embryonic region that develops into feet or hands is initially a solid platelike structure; then apoptosis eliminates the cells in the interdigital regions and forms the digits

DNA technology and other modern biochemical methods

enabled the researchers to test whether the biked product is in fact a morphogen that determines the anterior end of the fly; they first looked so see if the mRNA and protein products of these genes are located in the egg in a position consistent with the hypothesis; they found that biked mRNA is highly concentrated at the extreme anterior end of that mature egg as predicted by the hu[othesis; after the egg is fertilized the mRNA is translated into protein; the biked protein then diffuses from the anterior end toward the posterior resulting in a gradient of protein within the early embryo but the highest concentration is at the anterior end which is constant with the Biciod hypothesis which says that the bicoid protein specifies the flys anteriorr end

tumor supressor genes

encode proteins that help prevent uncontrolled cell growth, genes whose products inhibit cell division

more cells

equals more cells and that leads to tumor

why DNA can get damaged

exposed to ultraviolet light

stem cells derived from bone marrow precurosr could be

fat cells, bone cells, or white blood cells

goal for iPS

for the cells to provide tailor made replacement cells for patients without using any human eggs or embryos thus circumventing most ethical objections

adut brain

hads stem cells that continue to produce certain kinds of nerve cells there

fruit flies and other arthopods

have a modular construction composed of an order series of segments; these segments make up three major parts: the head, the thorax, and the abdomen

adult stem cells of bone marrow application

have been used as a source of immune system cells in patiants whose own immune systems are nonfunctional because of genetic disorder or radiation treatments for cancer

all cells in an organism

have the same genome

tumor supressor gene products

have various functions: some tumor suppressor proteins repair damaged DNA a function that prevents the cell from accumulating cancer causing mutations, other proteins control the adhesion of cells to each other or to the extracellular matrix; proper cell anchorage is crucial in normal tissues and is often absent in cancer, lastly other proteins are components of the cell signaling pathway that inhibit the cell cycle

segmentation

head, legs, wings, all on the right body plan and set up

Dolly

her chromosomal DNA was indeed identical to that of the nucleus donor

induced pluripotent stem cells

iPS cells, Researchers are able to reprogram fully differentiated cells to act like ES cells using retroviruses and those cells transformed this way are called iPS

naturally occuring clones

identical twins (they too are slightly different which shows environental influence and random phnemomia can play a significant role during development)

How do different sets of activators come to be present in the two cells?

in cells that are differentiated they have a particular mix of specific activators that turn on the collection of genes who's prepuces are required in the cell, it turns out that materials placed into the egg by the mother set up a sequential program of gene regulation that is carried out as cells divide and this prorgram makes the cells become different from each other in a coordinated fashion

Why are there low efficiency of cloning and high incidents of abnormality?

in the nuclei of fully differentiated cells a small subset of genes is turned on and expression of the rest is repressied; this regulation often is the result of epigenetic changes in chromatin such as acetylation of histones or methylation of DNA, during nuclear transfer procedure many of these changes must be reversed in the later stage nucleus from a donor animal for genes to be expressed or pressed appropriately in early stages of development; researches have found that the DNA in cells from cloned embryos like that of differentiated cells often have more methyl groups han does the DNA in equivalent cells from normal embryos of the same species; this finding suggests that the reprogramming of donor nuclei requires more accurate and complete chromatin restructing than occurs during cloning procedures; because DNA methylation helps regulate gene expression misplaced or extra methyl groups in the DNA of donor nuclei may interfere with the patterns of gene expression for normal embryonic development; the success of gene cloning depends on whether or not the chromatin in the donor nucleus can be artificially rejuvenated to resemble that of a newly fertilized egg

apoptisis pathways

in worms and other species opposites is triggered by signal transduction pathways; these activate a cascade of apoptic suicide proteins in the cells destined to die including the enzymes that break down and package cellular molecules in the blebs

genes that normally regulate cell growth and division during the cell cycle

include genes for growth factors, their receptors, and the intracellular molecules of signaling pathways; mutations that after any of these genes in somatic cells can lead to cancer; the agent of such change can be random spontaneous mutations however it is likely that many cancer causing mutations result form environmetal influence such as chemical carcinogens, X-rays, and other high energy radiation, and some viruses

gene amplification

increases the number of copies of the photo-oncogene in the cell through repeated gene duplication, this results in: normal growth stimulating protein in excess (normal growth of the protein but just excess protein) (increase in the amount of growth amplified growth promoting genes/proteins which pushes the cell to uncontrolled growth)

ras protein

is a G protein that relays a signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases; the cellular response at the end of the pathway is the synthesis of a protein that stimulates the cell cycle

the maternal effect gene

is a gene that when mutant in the mother results in a mutant phenotype in the offspring regards of the offsprings own genotype, this is because during fruit fly development the mRNA or protein products of meternal effect genes are placed in the egg while it is still in the mothers ovary; therefore when the mother has a mutation in such a gene she makes a defective gene product and her eggs are defective so when these eggs get fertilized they fail to develop properly

bicoid

is a gene, a term meaning two tailed, an embryo whose mother has two mutant alleles of the biked gene lacks the front half its body and has posterior structures at both ends; this suggests that the the biked gene is essential for setting up the antierior end of the fly and might be concentrated at the future antierior end of the embryo

stem cell

is a relativly unspecialized cell that can both reproduce itself infinitely and under appropriate conditions differentiate into specialized cells of one or more types

myoD protein

is a speficic transcription factor that acts as an activator (without the myoD gene is turned on then you become muscle cell off is no muscle cell)

organimsal cloning

is an organism that develops from a single cell without either meiosis or fertilization, it produces one or more organisms genetically identical to the parent that donated the single cell (In organismal cloning one or more organisms develop from a single cell without meiosis or fertilization The cloned individuals are genetically identical to the "parent" that donated the single cell)

in vertebrates apoptisosis

is essential for normal development of nervous system and for normal morphogenesis of hands and feet in humans and paws in other mammals (level of appetites is higher in land birds without webbed feet than ducks and other water birds with webbed feet) (in humans if we don't go through apoptosis then we have webbed hand and feet)

apoptisis in animals

is essential to develeopment and maintenance of all animals; there are similarities in genes encoding apoptptic proteins in nematodes and mammals and opposites is known to occur in multicellular fungi and single celled yeasts which is evidence that the basic mechanism evolved early amount eukaryotes

developmental potential of adult stem cells

is limited to certain tissues

cytoplasm of an unfertilized egg

is not homogenous; messenger RNA, proteins, other substances, and organelles are distrbuted unevenly in unfertlized egg, its uneveness has a prudent importance on the development of the future embryo in many species

first evidence of differentiation

is the appearance of mRNAs for the tissue specific proteins

apoptosis

is the best-understood type of "programmed cell death", it occurs in cells of developing organisms, also occurs in cells of the mature organism that are infected damaged or have reached the end of their functional life span, if this cell is no longer needed then cell death is programmed

pattern formation

is the development of a spatial organization of tissues and organs, cytoplasmic determinants and inductive signals both contribute to this (the development of a spacial organization in which the tissues and organs of an organism are all in their characteristic places), it begins in early embryo; In animals pattern formation begins with the establishment of the major axes; in bilaterally symmetric animal the relative positions of head and tail right and left sides and back and front (the three major body axes) are set up before the tissues and organs appear

medical application of stem cells

is to supply cells for the repair of damaged or diseased organs (ex: insulin producing pancreatic cells for people with type 1 diabetes or certain kinds of brain cells for people with Parkinsons disease or Huntigons disease)

determination term today

is understood as molecular changes

techniques used to study determination and differentiation of muscle cells

isolated different genes one by one, caused each to be expressed in a separate precurosr cell, and then looked for differentiation into my blasts and muscle cells

development of the fertilized egg

it is a single cell that becomes an embryo and later into an adult; takes a lot of astounding transformation that requires a precisely regulated program of gene expression

dropsphila axis

it is bilatrally symmetric so had an anterior-posterior (head to tail) axism a dorsal ventral (back to belly axis), and a right left axis`

bodh plan

its overall three dimensional arrangement

cytoplasmic determinants

maternal substances in the egg that influence the course of early development

mutations in tumor supressor gene and ras

mechanism causing cell growth and mechanism for not onto checking on to that cell growth

muscle cell determination

muscle cells develop form embryonic precursor cells that have the potential to develop into a number of cells types including cartilage cells and fat cells; certain conditions commit them though to becoming muscle cells; determination: signals from other cells leads to the activation of a master regulatory gene called myoD and the cell makes myoD protein then the cell is now called myoblast and is irreversibly committed to becoming a skeletal muscle cell, these cells appear unchanged but determination has occurred and caused them to become myoblasts, eventually my blasts start to churn out large amounts of muscle specific proteins and fuse to form mature eloganted multinucleate skeletal muscle cells; differentiation: myoD protein stimulates the myoD gene further and activates genes encoding other muscle specific transcription factors which in turn activates genes for muscle proteins then moD shuts off the cell cycle so no more division can take place and the non dividing my blasts fuse to become multinucleate muscle cells also called muscle fibers (factor that binds to specific control elements in the enhancers of varies target genes and stimulates there expression, some target genes for moD encode still other muscle specific transcription factors, moD also stimulates expression of the myoD gene itself thus perpetuating its effect in painting the cells differentiated state, since all genes activated by moD have enhancer control elements recognized by moD they are coordinately controlled, finally the secondary transcription factors activate the genes for proteins such as myosin and actin that confer the unique properties of skeletal muscle cells)

mutant cell cycle inhibiting pathway p53

mutations causing deficiencies in any pathway component can contribute to the development of cancer (ex; defective or missing transcription factor such as p53 cannot activate transcription of the protein that stops the cell cycle and so the inhibitory protein is absent and results: the cell cycle is not inhibited and there is increased cell division)

BRCA1

mutations in this gene is associated with increased sucscpetibility to breast cancer (BRCA stands for breast cancer), also the related gene BRCA2 is the same way

emrbyonic lethals

mutations with phenotypes causing death at the embryonic or larval stage

ras gene

named for rasarcoma a connective tissue cancer, codes for the Ras protein

p53 gene

named for the 53,000 dalton molecular weight of its protein product, is a tumor suppressor gene, the protein it encodes is a specific transcription factor that promotes the synthesis of cell cycle inhibiting proteins

cancer cell somatic mutation

need more than one somatic mutation to produce all the changes characteristic of a full fledged cancer cell; this is why incidence of cancer increases with age because mutations (which cancer comes from) increases as you age so the longer we live the more likely we are to have cancer

mutant cell cycle stimulating pathway Ras

normal a pathway will not operate unless triggered by the appropriate growth factor; but certain mutations in the as gene can lead to production of a hyperactive Ras protein that triggers the kinase cascade even in the absence of growth factor; this can lead to proteins being expressed and created all the time leading to over expression which results in increased cell division which can cause cancer, note that hyperactive versions/mutations or excess amounts of any of the pathways components can have the same outcome: excessive cell division

proto-oncogenes

normal versions of the cellular genes, codes for proteins that stimulate normal cell growth and division, is a gene that has an essential function in normal cells, genes whose products promote cell growth

reason to clone human embryos

not for reproduction but for the production of stem cells to treat human diseases

mutations in as but not in tumor supressor

nothing will happen because as long as tumor suppressor isn't damaged then nothing will happen and vice versa

outcome of determination

observable cell differentiation

mutations in the as photo-oncogene

occurs in about 30 percent of human cancers

difference between iPS and ES

occurs in cells in gene expression and other cellular function (like cell division)

mutations in the p53 tumor suppressor gene

occurs in more than 50 percent of human cancers

activites of a cell depend

on the genes it expresses and the proteins it produces

How might a proto-oncogene become an oncogene?

oncogenes arises from a genetic change that leads to an increase either in the amount of proto-oncogenes protein product or in the intrinsic activity of each protein molecule; both of these things changes how cells go through cell growth and division processes, the genetic changes hat convert porto-oncogenes to oncogenes fall into three main categories: movement of DNA within the genome, amplification of a proto-oncogene, and point mutations in a control element or in the porto-oncogene itself; all mechanisms can lead to abnormal stimulation of the cell cycle and put the cell on the path to becoming malignant

proper gene expression

orchestrating that by all cells is crucial to the functions of life

guardian angel of the genome

p53 gene is called that, p53 prevents a cell from passing on mutations due to DNA damage; 1. the gene is activated for example by DNA damage and the p53 protein functions as an activator for several other genes; often it activates a gene called p21 whose product halts the cell cycle by finding to cyclin dependent kinases allowing time for the cell to repair the DNA, 2. p53 also activates expression of a group of miRNAs which in turn inhibit the cell cycle, 3. p53 protein can turn on genes directly involved in DNA repair, 4. when DNA damage is irreparable p53 activates sucide genes whose proteins products bring about apoptosis

point mutation

point mutation in either 1. the promoter or an enhancer that controls a proto-oncogene causing an increase in its expression; results in normal growth stimulatn protein in excess, 2. (within the gene) in the coding sequence of the proto-oncogene changing the genes product to a protein that is more active or more resistant to degradation than the normal protein; results in hyperactive or degradation resistant protein (causes the cell to divide a lot quicker than normal)

nurse cells

produce more mRNA on one side so more proteins on one side and they lay out axis of the origins

cloning theme

product is identical to the parent

master regulatory genes

proteins products commit the cells to becoming skeletal muscle (ex: myoD; this gene encodes myoD protein which is a transcription factor that binds to specific control elements in the enhancers of varies target genes and stimulates there expression, some target genes for moD encode still other muscle specific transcription factors, moD also stimulates expression of the myoD gene itself thus perpetuating its effect in painting the cells differentiated state, since all genes activated by moD have enhancer control elements recognized by moD they are coordinately controlled, finally the secondary transcription factors activate the genes for proteins such as myosin and actin that confer the unique properties of skeletal muscle cells)

cytoplasmic determinants located in the unfertilized egg

provide positional information for the placement of the anterior posterior and dorsal ventral axies even before fetilization

reprograming cells to act like ES

researches have been able to turn back the clock in fully differentiated cells and reprogram them to act like ES cells; first done by mouse skin cells then accomplished using human skin cells and other organs or tissues, HOW: researchers transform the differentiated cels into ES cells by using types of viruses called retroviruses to introduce extra cloned copies of four stem cell master regulatory genes

differential gene expression

results from the genes being regulated differently in each cell type

scientists and stem cells

scientists want to isolate the stem cells from various tissues and grow them in culture, with the right culture conditions with a specific growth factor these cells from adult animals have been made to differentiate into multiple types of specialized cells (though they aren't as versatile as ES cell)

breast cancer

second most common cancer in the US, 230,00 women and some men annually get it and it kills 40,000 each year (5 to 10 percent of breast cancer patients inherit it)

dolly death

she suffered lung disease at age of 6 which is normally happens to much older sheep and died a premature death; this showed that her cells in some ways were not quite as healthy as those of a normal sheep possibly reflecting incomplete programing of the original translated nucleus

induction

signal molecules from embryonic cells cause transcriptional changes in nearby target cells (cells dividing a lot and results in cells being able to induce, influence, and talk to the other cells around it causing cells with certain types of determinants can tell cells to produce certain types of molecules and the molecules tell)

polyp

small begin growth in the colon lining, the cells of the polyp look normal but they divide unusually frequently

model organisms

species that are easy to raise in the lab and use in experiments, understanding the genetic underpinnings of development has progressed mainly by studying the process of the model organism (ex: the fruit fly Drosophila melanogaster; an adult fruit fly develops from a fertilized egg passing through a wormlike stage called a larva; at every stage gene expression is carefully regulated ensuring that the right genes are expressed only at the correct time and place

activators

specific activators that turn on the collection of genes who's prepuces are required in the cell

multistep model for the development of colorectal cancer

start off with normal colon epithethial cells; 1. loss of tumor suppressor gene APC (or other); thus leading to a smell benign growth called polyp, 2. activation of as oncogene (now they start to grow), 3 (causing more mutations). loss of tumor suppressor gene DCC; mow larger benign growth called adenoma, 4. loss of tumor suppressor gene p53, 5. additional mutations; now its militant tumor called carcinoma (shows that its multiple things to cause malignant tumor)

blastula stage

stem cells can be isolated from early embryos at a stage called blastula stage or its human equivilent the blastocyst stage

F. C. Steward

successful cloned a whole plant from single differentiated cells, they found that single differentiated cells taken from the root and incubated in culture medium could grow into normal adult plants which would be genetically identical to the parents, these results showed that differentiation does not necessarily involves irreversible changes in the DNA; in plant mature cells can dedifferentiate and then give rise to all specialized cell types of the organism

cancer and muitations

the development of a malignant tumor is paralleled by a gradual accumulation of mutations that convert photo oncogenes to oncogenes and knock out tumor suppressor genes ( a as oncogene and a mutated p53 tumor suppressor gene are often involved); about half a dozen changes (6) must occur at the DNA level for a cell to become fully cancerous; these changes usually include the appearance of at least one active oncogene and the mutations or loss of several tumor suppressor genes

gene cloning

the division of an asexually reproducing cell into a collection of gentically identical cells

homeotic genes

the genes lewis discovered and they control pattern formation in the late embryo, larva, and adult

morphogen gradient hypothesis

the hypothesis for where the biked gene is in the embryo is an example of the morphogen gradient hypothesis; gradients of substances called morphogens establish an embryo's axes and other features of its form

therapeutic cloning

the main aim of cloning is to produce ES cells to treat disease the process is called this, [people believe reproductive cloning of humans is unethical ut opimions vary about the morality of therapeutic cloning

thorax

the midbody from which the wings and legs extend

positional information

the molecular cues that control pattern formation, are provided by cytoplasmic determinants and inductive signals, these cues tell a cell its location relative to the body axes and to its neighboring cells and determine how the cell and its progeny will respond to future molecular signals

apoptisis role in developing embryo

the molecular mechanism of apoptosis were worked out in detail by researchers studying embryonic developmental of a small soil work which is a nematode called Caenorhabditis elegans that has now become a popular model organism for genetic studies; because the adult worm has only about 1000 cells the researchers were able to workout the complete ancestry of each cell, the timely sucicide occurs 131 times during normal development of C. elegant at precisely the same point in the cell lineage of each worm

transcription

the most important regulatory point for maintaining appropriate gene expression

conclusion of gardens experiment

the nucleus of a differentiated from cell can direct development of a tadpole (so something in the nucleus changes as animal cells differentiate) but its ability to do so decreases as the donor cell becomes more differentiated presumably because of the changes in nucleus

nucleear transplation

the nucleus of an unfertilized egg cell or zygote is replaced with the nucleus of a differentiated cell called nuclear transplantation

tissues to function propery in the organism as a whole

the orgs body plan must be established and superimposed on the differentiation process

morphogenesis

the physical process that gives an organism its shape, the development of the form of an organism and its structures

cell differentiation

the process by which cells become specialized in structure and function, the different kinds of cells are not randomly distributed but organized into tissues and organs in a particular 3d arrangement

What generates the first differences among cells in an early embryo? And what controls the differentiation of all the various cell types development proceeds?

the specific genes expressed in any particular cell of a developing organism determine its path

Christiane Nusslen Volhard and Eric Wiechaus

their goal was to identify all the genes that affect segment formation in the fruit flies

N and E experiemnt

they began their search for segmenetation genes by exposing flies to a mutagenic chemical that affected the flies gametes, the then mated the mutagenized flies and then scanned their descendants for dead embryos or lave with abnormal segmentation or other defects (ex: to find genes that might set up the anterior posterior axis they looked for embryos or larvae with abnormal ends such as two heads or two tails predicting that such abnormalities would arise from mutations in maternal genes required for correctly strong up the offsprings head or tail end), using this approach they indefitied about 1200 genes essential for pattern formation during embryonic development; of the about 120 were essential for normal segregation, they were then able to group these segmentation genes by general function to map them and to clone them for further study in the lab; the result of all this was a detailed molecular understanding of the earl steps in pattern formation in Drosphilia

cloned animals faults

they don't always look or behave identically to their parent (ex: certain cows are dominant behavior and others more submissive, nonidentiy example: CC for carbon copy was the first cloned cat, she has a calico coat like her single female parent but the color and pattern are different because of random X chromosome inactivation which is a normal occurrence during embryonic development) (they too are slightly different which shows environental influence and random phnemomia can play a significant role during development)

if scientists could clone human embrues to the blastocyst stage

they might be able to use such clones as the source of ES cells in the future; they could use a donor nucleus from a person with a particular disease and they might be able to produce ES cells for treatment that match the patient and are thus not rejected bu his or her immune system

scientist approach to see if animals cells could be totipotent

they remove the nucleus of an unfertilized or fertilized egg and replace it with the nucleus of a differentiated cell, if the nucleus from the differentiated donor cell retains its full genetic capacity then it should be able to direct development of the recipeant cell into all the tissues and organs of an organism (this was done on frogs)

cell division

through a succession of mitotic cell divisions the zygote gives rise to a large number of cells, cell division alone would merely produce a great ball of identical cells (nothing like a tadpole)

differential cells make

tissue specific proteins (ex: liver cells spexilizae in making albumin, lens cells make crystalline, skeletal muscle cells in vertebrates have high concentrations of muscle specific versions of the contractile proteins myosin and actin as well as membrane receptor proteins that detect signals from nerve cells)

cells are organized into

tissues, tissues into organs, organs into organ systems, and organ systems into the whole organism; thus any developmental program must produce cells of different types that form higher level structures arranged in a particular way in three dimensions

cloning mammals

to clone mammals they translated nuclei or cells from a

how to obtain ES cells

to harvest them from embryos which raises ethical and political issues; they are currently obtained from embryos by patients undergoing infertility treatment or from long term cell cultures originally established with cells isolated from donated embryos

Robert Briggs and Thomas King and John Gurdon

transplated a nucleus from an embryonic or tadpole cell into an enucleated (nucleus lacking) egg of the same species, in guardians experiment the transplaed nucleus was able to support normal development of the egg into a tadpole, he however found that the potential of a transplanted nucleus to direct normal development was inversely related to the age of the donor: the older the donor nucleus the lower percentage of normally developing tadpoles so the early embryo whose cells were relatively udiffererentiated produced the most development of tadpoles but when the nuclei me from the fully differentiated intestinal cells of a tadpole less than 2 percent of the eggs developed into normal tadpoles and most stop developing in an early stage, gudon then concluded that sometime in the nucleus does change as animal cells differentiate

gene regulation systems that go wrong during cancer

turn out to be the very same systems that play important roles in embryonic development, the maintenance of stem cell populations, and many other biological processes (thus research into the molecular basis of cancer has both benefited from and informed many other fields of biology)

differentiation is ovservable

with a microscope as changes in cellular structure

fertilized egg

zygote