Organs from Mesoderm (Lec. 66-67)

Types of Bone Cells

Chondrocytes and osteoblasts- Secrete cartilage and bone matrix, respectively Osteoclasts-function to resorb bone-These cells work with osteoblasts to regulate intramembranous ossification.

Bulbus Cordis

Divisible into three parts: Truncus arteriosus Conus cordis proximal parts of bulbus cordis

Dorsal Changes

Dorsal intersegmental arteries are what give rise to the arteries of the limbs

relationship of pharyngeal arch development and aortic arch system

Pouches: The indentation between arches overlying the endoderm Each Pouch Emanates from the Endodermal lining, giving rise to distinct organs. Each arch contains its own population of mesoderm and neural crest cells

Which surrounding mesoderm do the lungs grow into and what does it secrete during lung development

The lungs are covered by the *visceral mesoderm* which is activate by BMPs to secrete *noggin*

Examples of congenital heart defects

mixing or oxygen-poor systemic blood with oxygenated pulmonary blood involves narrowed valves or vessels (stenosis) ventricular septal defect, coarctation of the aorta, tetralogy of fallot

formation of cardiac D-loop

note bulbus cordis

What makes up a blood island

nulcleated red blood cells and endothelial cells that arise from VEGF activated mesodermal cells in a low oxygen situation.

overview of heart formation

primary heart field: the crescent of thickened cells at day 15 Day 21: folding along the dorsal-ventral axis causes the heart field to form a heart tube. blood gets pumped through this tube Day 28: aortic arches form from the aortic sac region and the atriums loop cranially. (externally they form the head stuff like the maxilla a mandible. internally they form the blood vessels etc.) Day 50: heart and blood vessels in place and pumping blood

Tube in tube body plan

take note of where the blue ectoderm is around the belly

mitral regurgitation

heart murmur

Hepatosplenic hematogensis and beyond

*Definitive Hematopoietic Stem cells (dHSCs) from mesoderm populate the liver ~day 23. dHSCs then migrate to the long bone marrow by week 10.*

Two Types of bone formation

*Endochondral ossification*-cartilage model forms first which then ossifies: Bones of the axial skeleton including vertebrae, ribs, sternum, cranial base, limbs *Intramembranous ossification*-bone forms from mesenchyme or neural crest cells: bones of the face and cranial vault

vasculogenesis vs angiogenesis cont.

*key*: growth of blood vessels is drivien by *low oxygen*. in times of low oxygen, cells secrete *Vascular Endothelial Growth Factor (VEGF)*. VEGF is *stable at low oxygen levels* thereby encouraging vascular development in areas of low O2. FGF2 alternatively, causes mesodermal cells to stay as mesoderm (not form hemangioblasts). All mesoderm cells have fibroblast growth factor receptors (FGFR) and VEGF receptors. There are 4 types of VEGF receptors (A-D) and VEGF A is further divided into 5 isoforms. Placenta Growth Factor (PLGF) is a member of the VEGF family.

Dev of Circ. System cont.

-Aortic Arch arteries (coming off heart) -Dorsal Aortic Region (ventral vitellin vessels; dorsal intersegmental branches, vertebral column, body wall, limbs -umbilical vessels region

Development of Arm Arteries

1) ~Eday 27, the Axial Arteries arise by Vasculogenesis from *somatopleuric lateral plate mesoderm*. 2. 2) ~Eday 30, the 7th *cervical* intersegmental arteries emanate from the dorsal aorta (angiogenesis) And anastomoses (cross connect) with the axial artery. 3) The axial artery then extends its growth concomitantly with the muscle progenitors and ventral and dorsal masses. Take home message: Identify how the arm becomes vascularized. Identify the mature arteries that develop directly from the axial artery. Brachial Artery upper arm Interosseous artery lower arm.

Pathway of blood in Fetus

1. oxygenated blood enters through umbilical vein, the *ductus venosus* shunts oxygenated blood away from the semifunctional liver and towarsd heart where it enters right atrium via inferior vena cava 2. the *foramen ovale* allows blood into right atrium 3. the *ductus arteriosus* connects the aorta with pulmonary artery, further shunting blood away from the lungs and into the aorta 4. mixed blood travels to head and body and back to placenta via aorta

Ventral changes (embryo - 1st tri)

29 days to 7 weeks the change that occurs: vitelline arterial plexus - ( a main *ventral* change.) to form three arterial branches of the abdominal gut. Celiac artery superior mesenteric artery Inferior mesenteric artery These arteries define the three regions of your gut

Turner Syndrome

A chromosomal disorder in females in which either an X chromosome is missing, making the person XO instead of XX, or part of one X chromosome is deleted. *blockages of lymphatics resulting in cystic hygromas. They often clear with age.* *puffiness, no folds of fat*

Congenital Heart Defects

Acyanotic: left to right shunts outflow obstruction Cyanotic: tetralogy of Fallot, transposition of the great arteries, atrioventricular

Milroy Disease

An autosomal dominantly-inherited disease that is characterized by lower-extremity lymphedema. The main cause is a paucity of lymphatic vessels. Inherited in an autosomal dominant. Characterized by lower-limb lymphedema Lymphoscintigraphy can be performed; the characteristic finding is lack of uptake of radioactive colloid in the lymph nodes caused by a paucity of lymphatic vessels or abnormal function of the vessels in the lower limbs.

Blood formation over time in embryo

Blood initially forms from the 2ndary yolk sac, and is quickly followed in utero within the Developing liver. *Definitive Hematopoietic Stem cells (dHSCs) from mesoderm populate the liver ~day 23. dHSCs then migrate to the long bone marrow by week 10.*

Day 21 and beyond

By day 35 you almost have the whole heart formed! (very fast) The fourth pharyngeal arch will form the aorta the dorsal and ventral aortas that are cranial go onto form the internal and external carotid arteries (respectively)

Lymphatic Development

Came from mesoderm ~6 weeks of development, endothelial cells from major veins undergo *bilateral angiogenesis* The jugular right and left lymphatic sacs form first. These sacs drain lymph from the upper limbs, trunk, head, and neck These sacs are followed caudally by growth of the subsequent retroperitoneal sac, The cisterna chyli, and the posterior sac By *8-9 weeks* the sacs mature into ducts. *The cisterna chyli serves as a central lymph basin that drains into the thoracic duct, Which empties into the venous circulation*

Blood formation within Embryo

First in yolk sac then in extraembryonic mesoderm Then in embryo A.EXM covers the endoderm of secondary yolk sac B.*Mesoderm* cells (both extraembryonic and embryonic) begin clustering and differentiating into hemangioblasts (blood islands that are angiogenetic) c.Further differentiation of hemangioblasts produce both the primitive blood cells and endothelial cells lining capillaries The outside cells of the blood islands will form endothelial cells and the inside cells will form primitive blood cells

Day 21 and beyond continued

Focus on day 21 and beyond The cranial region of the endocardial Tubes, once fused, form the Truncus arteriosus. By day 24 or so, the Truncus Arteriosis Becomes the aortic sac, which is then subdivided (by hox genes) into The aortic arch arteries. The aortic arch arteries then give rise to arteries of the head and neck From this image you can see that the main, dorsal Aorta arises from the 4th pharyngeal arch The dorsal and ventral aortas eventually become the internal and external carotid arteries, respectively.

Right After Birth Circulation

Hours to within 2-7 days after birth three key changes must occur for the new born's vasculature to adjust to a terrestrial environment 1.)The ductus arteriosus must constrict (forms the *ligamentum arteriosum*). Happens within 24hrs 2.)Umbilical vessels constrict and degrade 3.)The oval foramen must close -Controlled initially by increased pressure in left atrium and later the foramen is physically sealed shut (3-7 days)

Mesoderms and their final Organs

Intermediate mesoderm: kidney and gonds Paraxial (somitic) Mesoderm: -Head -Somite: sclerotome (cartilage and long bones of arm, eventually forms bones), syndotome (tendons), myotome (skeletal muscle), dermatome (dermis, skeletal muscle), endonthelial cells lateral plate mesoderm -Splanchnic (circulatory system) -Somatic (body cavity, pelvis, limb bones) -Extraembryonic

Summary

Mesoderm comes from ectoderm that has engressed through the primitive streak Convergence and extension of mesoderm in conjunction with inductive intercellular signaling results in segregation of mesoderm into three regions Paraxial, Intermediate, and Lateral Plate mesoderms The Lateral Plate mesoderm subdivides into the Somatic mesoderm (Dorsal) And the Splanchnic (ventral) mesoderm. Somatic mesoderm (don't confuse with somitic) begins to grow over the splanchnoplueric mesoderm forming the intraembryonic cavity Human development of mesoderm is basically a tube-within-a-tube body plan Heart formation is complex beginning with a primary heart field, followed by the heart tube, and eventually the four-chambered heart Development of the circulatory system is equally as complex as the heart. Be able to identify the arterial components, the venous components, and the process of blood development (vasculo vs angiogenesis) Be able to trace blood flow in the embryo, fetus, and soon after birth. The Mesenteries (mesoderm tissue) initially hold the gut tube in place. Later they serve as a site for endoderm-derived organs such as the liver to form. The mesenteries also develop into tissues such as the greater and lesser omentum. Somites are important structures. There are three functional parts to a somite Somites give rise to muscular and skeletal components within limbs Myotome- ventral and dorsal muscle masses form the muscles of the arms and legs Sclerotome-forms long bones via endochondral ossification Muscle masses begin to form by week 7 post fertilization. Epimere-Erector spinae, Hypomere-transversospinalis, hypaxials, rectus abdominous, Bone formation is accomplish two ways Endochndral ossification Intramembranous ossification

Fetal heart vessel formation

Note the yellow dots, these are found in fetal babies, but not in adults. if present in adults - bad.

Formation of Limb buds

Paraxial mesoderm Limb buds form from somatopleuric lateral Plate mesoderm. *Muscle progenitors migrate from the somitic myotome* and into the limb buds. The muscle progenitors for, the ventral and dorsal masses.

Formation of verntral and dorsal muscle masses

Paraxial mesoderm forms dermamyotomes within the somites. Mesoderm migrates to the limb buds that are forming from somatopleuric lateral plate mesoderm.

Parietal versus Visceral pleura

Parietal pleura is the pleura which lines the inside of the chest wall. Visceral pleura is the pleura which covers the surfaces of the lung. Between them there is normally a little lubricant fluid which allows the two layers to slide over one another easily during respiration. The pleural cavity is the thin fluid-filled space between the two pulmonary pleurae (known as visceral and parietal) of each lung. A pleura is a serous membrane which folds back onto itself to form a two-layered membranous pleural sac.

Embryo Circulation

Starting at placenta A) O2 rich blood flows from placenta through umbilical vein (9) B) Blood enters the heart tube (11) at the sinus venosus C) Blood enters the atrium and mixes with 02 depleted blood being delivered from common cardinal vein D) Blood flows through A-V Canal to Ventricle to Bulbus Cordis to Truncus Arterious E) Blood flows through aortic arches and diverts into the internal carotid artery flowing to head and dorsal aorta (6) F) Blood flows through aorta, some of which diverts to vitelline vessels, intersegmental vessels (5), and iliac vessels F1) the diverted blood then finds its way back to the heart through the posterior and anterior Cardinal veins , and vitelline vein (10). G) Large proportion of blood is shunted from aorta to the umbilical artery, which feeds back into the placenta

Fetal Circulation (month 5-9)

Starting with Placenta 1.)O2-rich blood flows from placenta through umbilical vein 2.)Half of the O2-rich blood is shunted through liver. The other half flows through ductus venosus bypassing the liver 3)The ductus venosus and inferior vena cava meet and carry bulk of blood to right atrium 4)Most of the O2-rich blood entering the right atrium from the IVC/DV is directed to the left atrium through the oval foramen (This will be sealed upon birth) -A small amount of IVC/DV blood is diverted from the right atrium to the right ventricle through the developing tricuspid valve. -Most of the blood from the superior vena cava that flows into the right atrium is pumped through the tricuspid valve and into the right ventricle. -The blood in the right ventricle is O2-medium enriched and flows to developing lungs and into the aorta via DA 5)The blood in the left atrium is mixed with a small amount of blood returning from the lungs via pulmonary veins and is then pumped through the developing mitral valve into the left ventricle. NOTE: Fetal lung blood is low O2 because the lungs are using O2 to develop 6)Blood is pumped from left ventricle to aorta where it eventually finds its way to the umbilical artery and back to the placenta

pericardial cavities

The intraembryonic cavity is the source for all of the cavities. Look at (B) Further growth of the embryo leads to folding of mesoderm around organs such as the heart and gut tube. 2) Follow the purple arrows to identify the formation of the pericardial cavity, the Parietal Pleura,and the pleural cavity. 3) Definitions: Pleura-the physical membrane (e.g., parietal pleura)

Development of Circulatory System

Vasculogenesis and angiogenesis persist throughout development This process gives rise to Arteries and Veins. Both the arterial and venous systems are subdivided into regions. Arterial system Aortic Arch region Dorsal aortic region -Ventral Vitellin vessel subregion (eventually supplies blood to GI Tract) -Lateral Branches (Kidneys and gonad blood supply) -Dorsal intersegmental branches (Vertebral column, body wall, and limbs) Umbilical vessels region Venous system Vitelline region Umbilical region Cardinal region (embryo)

Cardiogenic Area

area near the head of the embryo where the heart begins to develop 18-19 days after fertilization Lateral plate mesoderm which includes the splanchnic/splanchnopleuric will form the future circulatory system

Growth of heart

driven by *hemodynamic load* which pushes vessels and heart to grow Cardiomyocytes are proliferating in all chambers to cause heart growth (stops later in life). *Neuregulin* is one gene involved in this growth. Genes like these are becoming important to understand because they can be used in clinical trials to identify their ability to regenerate infarcted regions of the heart. Valves are important for proper direction of blood flow. They form first as regional swelling of *extracellular matrix* secreted from *cardiomyocytes*. These swelling are called cardiac cushions . The AVV (in blue) cushion is only fused with the LV at day 28. by day 50 the AVV cushions becomes the AVV. fibroblasts too

Vasculature of develoment

embryonic, fetal, and adult vasculature (changes in each stage) 1) Because of all the Looping, 2) Septation of vessels, 3) And its association with placental circulation. The embryonic folding video may help with the latter... More in-depth analysis of cardiac development Will be done in the CV Module.

Week 3-4

first organ to form is heart intermediate mesoderm begins forming earliest pregenitors for urogenital tract *somatic* mesoderm begins to grow over the splanchnopleuric mesoderm to form the intraembryonic cavity (coelom) not paraxial mesoderm and somatic mesoderm, splanchnopleuric mesoderm is in the entraembryonic cavity

Muscular Dystrophy

group of hereditary diseases characterized by degeneration of muscle and weakness *dystrophin protein is all messed up* this is the anchor fibers which myosin and actin generate power from. MD is a congenital defect within muscles. There are 9 clinical classifications of MD. Which type dictates the type of care that child will need Duchenne muscular dystrophy, which represents about half of all cases of muscular dystrophy, affects about one in 5,000 males at birth

Angiogenesis vs Vasculogenesis

vasculogenesis = mesoderm ------hemangioblasts----tube formation, endothelial cell to cell interactions angiogensis = pruning and remodeling and branching of 'juvenile' vascular system Two distinct mechanisms, vasculogenesis and angiogenesis implement the formation of the vascular network in the embryo. Vasculogenesis gives rise to the heart and the first primitive vascular plexus inside the embryo and in its surrounding membranes, as the yolk sac circulation. Angiogenesis is responsible for the remodeling and expansion of this network. While vasculogenesis refers to in situ differentiation and growth of blood vessels from mesodermal derived hemangioblasts, angiogenesis comprises two different mechanisms: endothelial sprouting and intussusceptive microvascular growth (IMG). The sprouting process is based on endothelial cell migration, proliferation and tube formation.

Mesodemal development of the rib cage

~ 5 weeks of development the costal processes (from *paraxial* *sclerotomes*) within the thoracic region elongate along the body wall ~ week 7 the first seven ribs connect ventrally and cranially to *mesenchymal condensates, also known as sternal bars*. which ossify to form the sternum. fusion proceeds caudally. During the fetal period and by birth, Mid-regions of the sternum have ossified,while the regions of the sternum connected to bone remain as cartilaginous. The xiphoid process does not ossify until birth 5 ribs caudal to the 7 true ribs do not fuse to the sternum. Theses are also called false ribs

Development of Leg Circulatory System

~Eday 35, the lower axial Arteries arise by vasculogenesis from somatopleuric lateral plate mesoderm (Similar to Arm) 1) ~ Eday 30, the 5th *lumbar intersegmental arteries emanate from the dorsal aorta and anastomose with the axial artery. 2) ~Eday 35 the Axis arteries grow quickly and become the *external iliac arteries*. This artery is the initial site for virtually all arteries of the leg (three exceptions : sciatic, popliteal, and fibular arteries). Take home message: Identify how the leg becomes vascularized. Identify the artery that develops directly from the axial artery external iliac artery