L2: Embryogenesis

Question 1

What parts of the nervous system does the neural tube different into? Neural crest?

Answer 1

• Neural tube becomes CNS, neural crest becomes PNS

Question 2

Where does implantation usually take place? What if this doesn’t take place?

Answer 2

• In the superior posterior aspect of the uterine wall. Failure of this to occur can lead to an ectopic pregnancy, which refers to implantation anywhere else but here. For example, this could occur in the Fallopian tube, cervix or abdominal cavity.

Question 3

Provide, in detail, the process of embryogenesis during week 2.

Answer 3

• The embryoblast develops into the bilaminar embryonic disc at week 2 (day 8), which consists of the hypoblast and epiblast. This ultimately gives rise to the germ layers that form all tissues and organs of the embryo - A small cavity that is the start of the amniotic cavity starts appearing in the embryoblast. Part of the epiblast differentiates into amnioblasts, which separate from the epiblast and begin forming the amnion that encloses the amniotic cavity. The epiblast forms the floor of the amniotic cavity with the amnion peripheral to it - During this time, invasion into the endometrial lining is still occurring. Lacunae appear in the syncytiotrophoblast. They become filled with mixture of maternal blood from ruptured endometrial capillaries and cellular debris from uterine glands. Erosion into spiral uterine vessels represents the beginning of uteroplacental circulation. Blood flows into lacunae making oxygen and nutritive substances available to extraembryonic tissue, deoxygenated blood is removed through endometrial veins. By day 10, the human embryo is completely embedded into the endometrium. - Cells migrate from the hypoblast to form the exocoelomic membrane that surrounds the blastocystic cavity (internal to the cytotrophoblasts, which is the second to last layer of all the structures discussed) now called the exocoelomic cavity. The remaining hypoblast is the roof of this cavity. The embryonic disk (still composed of hypo/epiblast) lies in between the two cavities - The exocoelomic membrane and cavity form the primary umbilical vesicle (older texts this is know as the yolk sac). Loose CT known as extraembryonic mesoderm form from cells of this vesicle (extraembryonic endodermal lining) and surround the amnion and umbilical vesicle - Day 12: Large cavities, known as extraembryonic coelomic spaces, form in the mesoderm and fuse to form the extraembryonic coelom that will become the chorionic cavity later - Extraembryonic mesoderm is still present after the formation of the extraembryonic coelom: immediately surrounding the cytotrophoblast and amnion is the extraembryonic somatic mesoderm and surrounding the umbilical vesicle is the extraembryonic splanchnic mesoderm - There is an area of invagination of the extraembryonic coelom known as the connecting stalk, which will serve as the area occupied by the umbilical cord in future development - The hypoblast continues to produce cells that migrate along the inside of the primary umbilical vesicle (aka exocoelomic cavity), gradually forming a new cavity called the secondary umbilical vesicle (aka the definitive yolk sac) causing the pinching off and disappearance of the primary umbilical vesicle - The extraembryonic coelom continues to grow during this time and forms the chorionic cavity that is embedded with the chorionic sac whose walls (chorion) are formed by the extraembryonic somatic mesoderm and the two layers of trophoblast: cyto- and syncytio- - The amniotic sac and the umbilical vesicle are analogous to two balloons pressed together at the site of the embryonic disc and suspended by the connecting stalk (space for future umbilical cord) from the inside of a larger balloon. - Day 12-14: Continued implantation occurs and the CT cells of the endometrium undergo decidual reaction, which is the accumulation of glycogen and lipids in their cytoplasm. This reaction provides an immunological privileged site for the conceptus. This is the maternal contribution to the placenta. Cytrotrophoblasts proliferate and penetrate into the syncytiotrophoblast formed cell columns with syncytial covering known as primary chorionic villi.

Question 4

Gastrulation: What is the main purpose?

Answer 4

• The purpose of gastrulation is to form the 3 germ layers for embryological development ie. the ectoderm, endoderm and mesoderm

Question 5

What are somites and how do they relate to the adult form?

Answer 5

• Somites refer mesodermal embryonic tissue that arise from structures known as paraxial mesoderm that are bilateral to the notochord and neural tube. In the 4th week of embryogenesis, they form 3 segments: 1.) sclerotome that develop into the vertebrae and ribs; 2.) myotome that develop into limbs and trunk muscles and 3.) dermatome that develop into the dermis layers of skin

Question 6

Provide, in detail, the process of embryogenesis during week 1.

Answer 6

• Oocyte is released from the ruptured follicle and travels into the Fallopian tube where it is fertilized by a sperm - Zygote is formed when the sperm and egg unite and form a single cell - Zygote undergoes cell division without growth and the individual blastomere cells that form as a result become smaller and smaller. This proceeds to the 16 cell stage by day 4, this structure is called the morula - Morula develops into the blastocyst, which consists of an inner cell mass (ICM aka embryoblast is destined to become the embryo), outer cell mass (aka trophoblast is destined to become the placenta) and blastocystic cavity - At day 6-7, the blastocyst begins the process of implantation into the uterine wall. The trophoblast differentiates into syncytiotrophoblast (multi-nucleated mass) and cytotrophoblasts. The syncytiotrophoblast secretes enzymes to assist with invasion into endometrium and synthesizes/secretes b-HCG. Cytotrophoblasts continue to divide and form cells that migrate and contribute to the syncytiotrophoblast

Question 7

Provide brief summary of events of embryogenesis during week 2:

Answer 7

• implantation has just occurred - embryoblast forms epiblast and hypoblast, which is the bilaminar embryonic disc - cavity appears in embryoblast = amniotic cavity forms from epiblast and amnioblasts - uteroplacental circulation established - day 10: completely embedded embryo - cells from hypoblast to blastocystic cavity form exocoelomic cavity - exocoelomic cavity becomes primary umbilical vesicle - primary umbilical vesicle lining forms extraembryonic mesoderm - extraembryonic coelomic spaces form in mesoderm and fuse to form extraembryonic coelom that surrounds amniotic cavity and primary umbilical vesicle - connecting stalk is present - hypoblast produces cells that form secondary umbilical vesicle, pinching off primary umbilical vesicle, which disappears - extraembryonic coelom grows and forms chorionic cavity (walls = extraembryonic mesoderm and trophoblast layers) - day 12-14: endometrium undergoes decidual reaction, immunologically privileged site setup - placental villi formed

Question 8

Gastrulation: Highlight the steps:

Answer 8

• Epiblast becomes all three germ layers - Thickening epiblast median plane, formation of primitive streak, formation of primitive groove, formation of primitive node with pit - Cells from epiblast migrate to hypoblast, displace and become endoderm - Cells from epiblast migrate and become mesoderm - Mesoderm forms notochord - Notochord signals formation of neural plate, neural folds come together, neural tube forms separates from ectoderm, neural crest forms, ectoderm forms epidermis - Mesoderm forms paraxial mesoderm bilaterally to neural tube with intermediate and lateral mesoderm - Paraxial mesoderm becomes somites, which form axial skeleton, musculature and dermis - Intraembryonic coelom forms in lateral mesoderm, becomes larger and causes separation into two layers: splanchopleure (visceral/ventral layer with endoderm) and somatopleure (parietal/dorsal layer with ectoderm) - Splanchopleure develop into gut wall, somatopleure forms body, intraembryonic coelom forms 3 body cavities: pleural, pericardial, peritoneal

Question 9

As a result of gastrulation, what adult structures do the 3 germ layers develop into?

Answer 9

• Ectoderm: epidermis (hair, skin, nails), nervous system (CNS, PNS), retina, medulla adrenals - Mesoderm: dermis, muscle, connective tissue, bone, heart, arteries, veins, lymph vessels, vertebral discs (nucleus pulposus=notochord remnant), body wall, urogenital system (not bladder though), spleen, cortex of adrenal glands - Endoderm: epithelial lining of GI tract, respiratory tract and urinary bladder, thyroid, liver, pancreas

Question 10

What is neurulation? How is it different from the formation of the notochord?

Answer 10

• Neurulation refers to the development of the neural tube, which forms nervous system tissue, ie. central and peripheral. The neural tube is derived from the ectoderm germ layer. Formation of the notochord occurs prior to neurulation, and this structure is derived from the mesoderm germ layer. This structure has many important functions, including: acting as the caudal-cranial axis for the developing embryo, forms the basis for the axial skeleton and induces the ectoderm to undergo neurulation, formation of the neural tube and therefore nervous system.

Question 11

Provide, in detail, the process of embryogenesis during week 3-4.

Answer 11

• The start of week 3 marks the beginning of gastrulation, which is the conversion of the bilaminar embryonic disc into a trilaminar embryonic disc, ie. the formation of 3 germ layers (all from the epiblast): ectoderm, mesoderm, endoderm - The epiblast undergoes proliferation and migration and a thickened band known as the primitive streak appears caudally in the median plane of the dorsal aspect of the disc. - The primitive streak elongates through proliferation, including proliferation at the cranial end to form a primitive node. A groove develops in the primitive streak and ends in a depression at the primitive node known as the primitive pit (cranial end). - The embryo now has a craniocaudal axis, which divides right from left - Cells different and migrate from the epiblast (mesenchymal cells) and move ventrally and laterally. Some displace the hypoblast creating the endoderm and some lie between this newly created endoderm and epiblast to form mesoderm. Cells remaining in the epiblast form ectoderm. - Cells rapidly proliferate laterally and cranially. - Some mesenchymal cells (part of mesoderm) migrate cranially on median plane from the primitive node and pit, forming the notochord. This acts as a primary inductor, serving as basis for development of axial skeleton and indicating site of future vertebral bodies (becomes nucleus pulposus It also induces the overlying ectoderm to form the neural plate, an area of thickening in the ectoderm, which gives rise to the CNS. - The neural plate invaginates along the median plane and formals neural folds on either side. These folds are prominent on the cranial end and indicated first signs of brain development - By the end of the 3rd week, the neural folds merge creating the neural tube (neurulation), which soon separates from the ectoderm. The ectoderm now differentiates into the epidermis of the skin - While the neural folds were merging, some ectodermal cells along the crest of the fold merge to become what is called the neural crest. These lie on either side of the neural tube underneath the overlying ectoderm (becoming epidermis) - These neural crest cells migrate widely within the mesenchyme (mesoderm) and differentiate into many cell types including PNS, melanocytes, facial bones etc. - The mesoderm on either side of the neural tube and notochord proliferates to for columns called the paraxial mesoderm (bilaterally), which thins into lateral mesoderm. The lateral mesoderm is continuous with extraembryonic mesoderm (splanchnic? probably) that covers the umbilical vesicle and amnion - By the end of the third week, the paraxial mesoderm differentiates into somites – these are prominent by the 4th week and determine embryo’s age - The somites extend craniocaudally and give rise to most of the axial skeleton and the associated musculature and dermis of skin. During week 4, they specifically form 3 segments: a.) sclerotome, which form vertebrae and ribs; b.) myotome, which form limbs and trunk muscles and c.) dermatome, which forms the dermis of the skin - The intraembryonic coeloms appear in the the lateral mesoderm that enlarge to divide this area into two layers: a.) the somatopleure (ectoderm plus lateral mesoderm), which forms the body wall and b.) the splanchnopleure (endoderm plus lateral mesoderm), which forms the wall of the gut. The intraembryonic coelom becomes the three body cavities: pericardial, pleural and peritoneal. This folding typically occurs during week 4

Question 12

What is the difference between trophoblasts, cytotrophoblasts and syncytiotrophoblasts?

Answer 12

• trophoblasts: refer to the outer cell mass of the blastocyst and different into cytotrophoblasts and syncytiotrophoblasts - cytotrophoblasts: these are differentiated trophoblasts that merge with and support the growing mass of syncytiotrophoblast and also form primary chorionic villi, which are structures of the placenta that contain branches of the umbilical vein and arteries - syncytiotrophoblast: is a multi-nucleated mass without cellular boundaries that is differentiated from trophoblasts. It synthesizes and secretes enzymes that assist with invasion of the blastocyst into the endometrium. In addition, it also synthesizes HCG that maintains the uterus for the conceptus

Question 13

What is Spina Bifida? What are the 4 types?

Answer 13

• Spina bifida is a (neural tube defect-NTD) condition where the caudal aspect of the neural tube fails to close properly during the 1st month of pregnancy. If neurological defects are present, 80% in L&S regions, ie. weakness, paralysis, loss of sensation lower to area of lesion, loss of bowel/bladder ctrl. There are 4 different severities: - A.) Spina bifida occulta (hidden): defect in vertebral arches (lack of fusion) that is covered by skin and normally does not involve neural tissue. Affects 10% of otherwise normal people. Not usually detected at birth, often no disability results. - B.) Spina bifida with meningocele: mening = membrane, cele = herniation. Bone is un-fused, meninges protrude through back, covered by skin/membranous sac, may or may not result in neuro deficits - C.) Spina bifida with meningomyelocele: myel = spinal cord. Herniation of both spinal chord and meninges, membranous sac covers, neurological deficits present - D.) Spina bifida with myeloschisis: chisis = cleaving. Neural tube note closed at all, open spinal cord with no covering, worst of all spina bifidas - *B, C, D referred to as spina bifida cystica

Question 14

How does the intraembryonic coelom develop? What is its role in division of the lateral mesoderm (lateral plate)?

Answer 14

• The intraembryonic coelom begins as a cavity within the lateral mesoderm bilaterally to the notochord and neural tube. As this cavity becomes larger, the lateral mesoderm is separated into ventral (visceral) layer with endoderm known as the splanchopleure and dorsal (parietal) layer associated with the ectoderm known as the somatopleure. The splanchopleure forms the lining of the gut tube and the somatopleure forms the outer body wall.