Germ Layers I and II

Explain how defects in neural crest cells lead to Fetal Alcohol Syndrome

Some of the problems caused by exposure of the embryo to high alcohol, result from neural crest defects. e.g. Facial abnormalities are due to deficiency of neural crest cells. Children also commonly exhibit heart defects.

Describe the tissues that are derived from the somites.

The somite contains the precursor cells of 3 different tissues - myotome, dermatome and sclerotome. 1) *Sclerotome*: First, the lower medial portion of the somite breaks down and migrates away to form sclerotome (after receiving signals from the notochord), which will go on to form vertebrae and ribs. 2) The remaining tissue (minus sclerotome) is called dermamyotome. The dermamyotome then dissociates into *dermatome*, which will form: a/ the dermis (the underlying layer of the skin) b/ *myotome*, which makes the body muscles

Major objective

To understand the differentiation of different tissue types from the primary tissue layers (germ layers) of the embryo. To identify tissues generated from the somites and to understand the role of neural crest cells.

Major Objective

To understand the formation of the muscular tissues of the embryo and the origins of the primary blood vessels. Also, the folding events leading to the formation of the gut tube.

Explain the differences between formation of blood vessels by vasculogenesis and angiogenesis

Vasculogenesis is only responsible for making the major blood vessels in the embryo. All subsequent formation of blood vessels, including the provision of a blood supply to previously avascular tissues like the brain, is achieved by branching and extension from the primary vessels. This growth from pre-existing vessels is called angiogenesis.

*Lateral Mesoderm Layers

a). The somatic mesoderm (parietal mesoderm) in contact with ectoderm. This will form tissues of outer body wall, including connective tissue, bone, fat and tendons. b). The splanchnic mesoderm (visceral mesoderm) in contact with endoderm. It contributes smooth muscle, mesothelia and supportive tissues of gut organs (e.g. liver, lungs etc) and the heart muscle.

Describe the differences between skeletal, smooth and cardiac muscle

*Skeletal* Skeletal muscle arises from the myotome component of the somites. Limb muscle forms from mesenchyme surrounding the developing bones. These mesenchymal cells migrated into the limb buds from the myotome layer of the somites. Regular pattern = comes from somite *Smooth*: answerable to nobody: NOT ON EXAM a. Smooth muscle of the gut tissues is derived from the splanchnic mesoderm layer. b. For most blood vessels, smooth muscle comes from the somatic mesoderm. c. Smooth muscle of the iris, sweat glands and mammary glands comes from the ectoderm. d. For the ascending aorta and carotid vessels, smooth muscle is derived from migrating neural crest cells. !!! Smooth muscle development also involves a myoblast precursor cell. Smooth muscle cells do not fuse but remain *mononucleate*. *Cardiac* Cells that will form heart muscle (myocardium) arise from the splanchnic mesoderm in the cardiogenic region. This is sometimes called the cardiac crescent. !!! No fusion of cardiac muscle cells occurs. The myogenic determination genes are NOT involved in cardiac muscle differentiation. Separate evolution to skeletal muscle.

Integrate the interactions between different embryonic tissues and organs during early development.

1) Notochord sends out signals for tissue differentiation Ex: - sclerotome breaks away from somite wall - epiblast -> neural tissue 2) Closeness defines cell identity ex: - somatic mesoderm (close to ectoderm) becomes bone, fat, tendons (outer body wall) - splanchtic mesoderm (close to endoderm) becomes smooth muscle, mesothelia and supportive tissues of gut and heart 3) Signals downwards towards endoderm: signals sequential differentiation of gut organs - For the dorsal pancreas, signals from the notochord are required to induce expression of pancreatic regulatory genes.

Describe two examples of segmentation in the human embryonic body plan.

1) Somites: repeating structure (makes vertebrae) 2) Neural segments: The rhombomeres of the hindbrain are segmental structures Note repeating units of rhombomeres r1-r7

Differentiation of non-neural ectoderm

Apart from neural tissues, the embryonic ectoderm forms a number of other tissues including: a). Epidermis of the skin, including hair and nails. b). sensory epithelium of the ear and nose and the lens of the eye. c). the sweat glands, mammary glands and pituitary gland. d). the enamel of the teeth. So recap: pulp of teeth - neural crest. enamel - skin. If you can see it, it's ectoderm.

What are neural folds?

At about 18 days, the neural plate becomes visible as a distinct region on the surface of the embryo. Through a combination of cell proliferation and cell movements, the neural plate becomes larger and starts to fold. The edges of the neural plate are called the *neural folds*. => Will become the brain.

Explain how defects in neural crest cells lead to neurofibromatosis

Disease of neural crest cells affecting about 1 in 4000 individuals - *defect of NF1 function (ras family protein)*. Neural crest derivatives throughout the body may grow tumors. Although tumors are mostly benign they are disfiguring and they can press on nerves and cause extreme pain. More commonly revealed as pigmentation defects- café au lait spots (what cell type causes these?) Melanocytes!

Explain how defects in neural crest cells lead to Treacher -Collins Syndrome

Facial abnormalities due to *deficiency of neural crest cells* (undergo apoptosis): deficiency of the bones of the face.

Explain the embryonic origins of anencephaly and spina bifida.

Failure of the neural tube to fuse correctly results in rather common birth defects, generally called neural tube defects (NTDs). a. *Anencephaly* is caused by failure to fuse at the *cranial* end. b. *Spina bifida* is caused by failure to fuse at the *caudal* end. Folic acid deficiency has been implicated as a cause of NTDs, although the mechanism is obscure.

Describe the lateral and sagittal folding that results in formation of the tubular embryo

Growth of the posterior tissues produces a fold that causes the embryo to arch into the amniotic space. Together the folding movements of the head and the tail produce the foregut, midgut and hindgut. *Lateral folding* occurs primarily due to growth of the somites. These movements enclose the endodermal tissue, leaving only the vitelline duct as a connection to the yolk sac. The endodermal layer becomes completely enclosed in the splanchnic mesoderm layer to form the gut tube. Mesoderm extending between the gut tube and the dorsal body wall forms the dorsal mesentery.

Describe the major steps in formation of the heart

Image: heart starts off as a halo around your head, then moves towards the center to be at your chest (endocardial tubes) Cardiac precursor cells remain close to the endoderm. A signal from the endoderm is essential for heart development. Each heart primordium forms something like a simple blood vessel, with a vascular layer (the endocardium) surrounded by the myocardial layer. The two heart primordia are brought together by the lateral folding of the embryo and they fuse at the midline. One gene essential for heart development is called Nkx2-5. It is related to the tinman gene of Drosophila. Related genes are involved in heart development in all organisms.

Describe the formation of the neural plate.

Key takeaway: signaling from one embryonic tissue (ex: notochord, a mesoderm tissue) can affect the development of adjacent tissues (ex: the epiblast, an ectoderm tissue, to become neural) -> increases the complexity of the embryo Initially the ectoderm is an undifferentiated layer of tissue overlying the mesoderm. In response to signaling from the notochord, a region of the ectoderm is induced to form neural tissue. This tissue is called the *neural plate* and will develop into the central nervous system (brain and neural tube). Peripheral neurons will grow out from the neural tube during later development.

Describe how defects in embryonic folding may result in human disease

Meckel's diverticulum A bulge or pouch off the small intestine. Remnants of the yolk sac stalk. Present in 1 in every 50 people. Most people show no symptoms, although intestinal blockage or bleeding may sometimes result.

*Muscle Precursors

Skeletal muscle precursor cells are called myoblasts. These cells express myogenic determination genes. These transcription factors will regulate expression of the structural proteins of muscle (e.g. actin, myosin, tropomyosin etc.) Myoblasts migrate to the site of muscle formation. *Single myoblast cells fuse into multinucleate myotubes*. Myofibers containing contractile proteins then assemble.

Describe the primary derivatives of neural crest cells.

Neural crest cells differentiate into most of the tissues of the face, including the bones of the face. The bones illustrated in blue are derived from neural crest cells. Bones in red are derived from anterior somites and somitomeres. Depending on their final destination, neural crest cells develop into the following cell types: a). most of the bones and cartilage (but not the muscles) of the face b). pigment cells (melanocytes) c). tooth papillae (pulp tissue and dentine inside the enamel layer). d). connective tissue of the aortic arch arteries and the septum separating the aorta and the pulmonary artery.

* Neural crest cells' migration

Neural crest cells do not begin to migrate until the neural tube is closed. Then migrate away from neural tube, down the ectoderm. Cells migrate through the pharyngeal arches.

* Describe the formation of the neural crest cells.

Neural crest cells originally develop at the crests of the neural folds, a position that also marks the extreme lateral edges of the neural tissue.

Explain how defects in neural crest cells lead to Waardenburg syndrome

Note facial alterations and region lacking pigmentation in the hair. At the molecular level, mostly due to *defects in Sox10 or Pax 3 genes*.

What is the neural tube?

Precursor: neural groove In the developing chordate (including vertebrates), the neural tube is the embryo's precursor to the central nervous system, which comprises the brain and spinal cord Neural tube closure first occurs in the middle of the embryo and then proceeds cranially and caudally.

Explain the relationship between heart and liver development

Signals from the developing heart are required to induce liver formation. Note the proximity of the heart and the liver primordium

*Development of skeletal system

The axial skeleton is formed from scleretome. For the backbone, scleretome cells surround both the notochord and the neural tube. These cells then differentiate into bone. Bone in the limbs is generated from mesenchymal cells (schleretome) that migrate into the limb bud. These form cartilage and then bone.

Explain the relationship of somitomeres to somites.

The mesoderm closest to the notochord forms epithelialized balls called somites. Somite formation involves a transient intermediate structure called the somitomere. All except the 7 cranial-most pairs of somitomeres go on to form somites --> somitomere ( loose balls) become tighter and tighter = somites Somite formation commences cranially and progress caudally. TAKE AWAY: somitomeres = become facial muscles somites = body muscles and vertebrae

*Mesoderm differentiation

The mesoderm, lateral to the notochord, is divided into paraxial mesoderm, intermediate mesoderm and lateral mesoderm at increasing distances from the midline. The paraxial mesoderm forms the somites, repeating structures that form the primitive musculature of the embryo. The intermediate mesoderm will form the urinary system and reproductive system. The lateral mesoderm splits into two layers (see below)