Human embryology week 4

Human embryology week 4

1. Dorsal view 14 days old:

   • Anterior-posterior difference is already visible!
   • Surface of epiblast is not uniform, different between anterior and posterior difference because of primitive streak.
   • Primitive streak evident in posterior region; “groove” along dorsal surface of the epiblast; marks the beginning of gastrulation
   • 14 day human embryo has an Anterior-Posterior axis Q: What specifies the AP axis?
     • A: Small group of hypoblast cells determine anterior of epiblast
   • Epiblast and hypoblast form bilaminate embryo

2. Human embryology informed from the mouse

   • Until this point they look identical in both species
     • Mouse gestation is 18 days in lengths
   • A day later you have a cup shaped embryo
     • visceral endoderm is the same as hypoblast just in mice instead of humans become different at the visceral tip
       • Cells at distal tip of visceral endoderm (DVE) migrate to one side: active process
         • These cells determine the Anterior side of the epiblast
   • • AVE defines the future anterior end of the embryo
       • DVE cells move: form Anterior Visceral Endoderm
         • DVE/AVE cells express Lefty1 and Cerberus
       • AVE secretes two key signalling molecules (Lefty and Cerberus 1) that inhibit “posterior” markers (Nodal) in the anterior epiblast
         • AVE: expresses Lefty1 and Cerberus: inhibit Nodal activity in epiblast therefore this region becomes anterior (head)
           • Nodal activity is required to form posterior structures: Epiblast furthest from AVE can form primitive streak

3. Hex gene expression

   • Hex is expressed in the distal/anterior visceral endoderm
   • Regulatory control region (enhancer) that is required for this expression was identified
   • That enhancer can be used to control ‘reporter genes’ so they have the same expression pattern
   • Dark patches on images is where HEX is expressed
     • Expressed in the distal and and then anterior exoderm
   • Studying the movemnet of the anterior visceral endoderm
     • An approach used:
       • Green protein expressed in cells where Hex would normally be expressed
         • Green protein expressed in cells where Hex would normally be expressed
           • Movement of the distal/anterior visceral endoderm cells
             • These cells migrate up, until they reach boundary between embryonic endoderm Direction determines position of the embryo
   • Active migration of the distal/anterior visceral endoderm cells
     • How are they moving in this way:
       • Cells are extending phylopodia
         • Almost like cells are searching where to go
           • searching for preferable environment in the cell
             • Cell body moves following the phylopodia
   • Movement of the anterior visceral endoderm
     • Viseral endoderm cells position deremine where anterior is
       • When cells are migrating they are changing the localisation of cell membrane porteins and changing interacting with neighboring cells needed for Pilopodial extension to sense environmenent

4. Signalling from nodal: a TGFBeta family member:

   • Nodal precursors: cleaved by furin
     • Nodal binds to type I-II receptors, with EGF-CFC co-receptors (cripto)
       • Activated receptors phosphorylate SMAD2 & 3, downstream effectors
         • Activated SMADs associate with co-SMAD, SMAD4
           • Translocate to nucleus
             • Act with co-factors to stimulate target gene expression eg. Pitx2
               • SMAD2-3 degraded: ubiquitinylation

5. Establishing A-P axis in humans

   • Nodal activity in epiblast determines “posterior” At anterior end of epiblast, Nodal activity is blocked: therefore becomes “anterior”

6. Gastrulation

   • Formation of the Node and the Primitive Streak marks the beginning of gastrulation
     • Epiblast cells migrate towards the Node and Primitive Streak
       • Epiblast cells move through the Primitive Streak  leave the epiblast
         • First cells insert into and displace the hypoblast/visceral endoderm: form the definitive endoderm
           • Later epiblast cells form mesoderm (between endoderm and epiblast)

7. Epiblast cells change shape

   • And when they migrate through the primitive streak, they have to undergo this process of epithelial to mesenchymal transformation,
     • they have to go through a process called De-Lamination because they are leaving this laminar layer.
       • the first ones insights into the visceral enter doesn't quite fit last and become endothelial cells which are also epithelial in that type.
         • course the first ones insights into the visceral enter doesn't quite 1:11:53 fit last and become endothelial cells which are also epithelial in that type.
           • the cells all have to to migrate through the proton stream to come out underneath the cells from either methadone or and they're done.

8. Incomplete gastrulation

   • Gastrulation is required to form the 3 germ layers of the embryo, which are needed to form all subsequent tissues in the fetus
   • Complete failure of gastrulation : developmental arrest and death
   • Partial failure of gastrulation (incomplete gastrulation) causes caudal regression / sacral agenesis
   • Lower parts of body do not form [completely] if later events of gastrulation fail

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