01. Embryology

• once released, the egg is only viable for a maximum of 24 hours
• the potential for dizygotic twins occurs once the egg is released from the follicle and captured on the ends of the fallopian tube
• two pronuclei come together after fertilisation to form the diploid zygote
• sperm contributes the centriole as well as genetic material. This centriole organises the mitotic spindle that draws two nuclei together for DNA recombination
• the oocyte contributes mitochondria as well as genetic material
• the zona pellucida is the glycoprotein coat around the outside of egg, and this is where the sperm binds to. Fusion leads to a cortical reaction to block polyspermy.
• When the fertilised egg begins to divide this where the potential of monozygotic twins occurs. This occurs most commonly at the blastocyst stage.

  • if this occurs post implantation this forms conjoined twins.
• the fertilised egg eventually forms a morula and then enters the uterus. This is where the blastocyst forms and implants into the uterus.
• compaction = where the blastocyst loses totipotency. Polarity occurs resulting in the formation of the inner and outer cell mass.
• the inner cell mass is the cells that form the embryo
• the outer cell mass is the trophectoderm, forming the placenta.

  • outer cell mass pumps in fluid forming a blastocoel within the blastocyst.
• trophoblast cells differentiate to invade the epithelium.

  • syncytiotrophoblast = external layer without intercellular boundaries, forming a syncytium. Invades into the endometrium.
  • cytotrophoblast = irregular level of ovoid mononucleated cells that lies directly below the syncytiotrophoblasts
• gastrulation = go from being bilaminar to trilaminar, indicated by the appearance of a primitive streak and a primitive node.

  • occurs at around 15 days.
  • cells of the epiblast migrate towards the primitive streak and slip underneath it.
  • cells left in the epiblast form the ectoderm
  • cell migrating in between the epiblast and hypoblast form the mesoderm.
  • cells displacing the hypoblast form the endoderm.
• gastrulation is controlled by FGF8 which is synthesised by primitive streak cells.

  • downregulates E-cadherin which allows cells to become motile.
  • regulates BRACHYURY which allows epiblast cells to turn into mesoderms.
• the notochord will eventually form the spinal cord
• notochord formation occurs in a cranial to caudal sequence
• the notochord is an important site of signal secretion for nervous system development.
• NODAL maintains the primitive streak (produced by the primitive node) - regulates genes including:

  • BMP4 - stimulates formation of skin from ectoderm.
  • chordin, noggin - block BMP4 in some regions, nervous and cranial formation.
  • goosecoid/GSC - stimulates production of Cerberus which is important for head development.
• at 18 days the embryo has a distinctive notochordal plate and narrowing of the caudal end
• proliferation of cells from the primitive node forms a cord of cells in the median plan until it forms the prechordal platefollowed by notochordal-endodermal fusion

  • pinches off to form the definitive notochord within the mesoderm
• at 19 days the neural plate forms at the cranial end of the embryo, this folds over at day 20 to encapsulate the brain.

  • there is also emergence of somites from the mesoderm, these fuse later on at the fifth somite, then fusing upwards cranially and caudally
  • leads to encapsulation of the spinal cord
• neuropores form at the top and bottom of the embryo, these close at day 28

  • at day 28 there is emergence of other organs, the umbilical cord and heart bulge
• the notochord communicates with floor plates of the neural groove to release sonic hedgehog, this patterns the ventral neural tube
• from the roof cells there is release of BMPs which pattern the dorsal neural tube

  • chordin and noggin block BMP4, allowing the nervous system and cranial structures to form
• neural crest cells express MSK1/2 and snail2, these migrate away and interact with the cells from the mesoderm and ectoderm
• the first phase of differentiation of somites is segmentation. These segmented blocks of somites progressively appear from the anterior end.
• somites give rise to dermatome (dermis), sclerotome (muscle) and myotome (tendons, cartilage and bones)
• mesoderm:

  • paraxial mesoderm = somite formation
  • intermediate mesoderm = urogenital system
  • lateral plate mesoderm = visceral mesoderm (wall of gut tube) and parietal mesoderm (dermis of body wall, limbs, bones and connective tissue)