Early Mouse Development

Early Mouse Development

1. MODEL ORGANISM

   • CONS
     • small
     • slow development
     • in utero -> inaccessible to exp. manipulation
   • PROS
     • typical of MAMMAL embryology
       • Universal: fert->cleavage->gastrulation->organogenesis
     • mouse genetics well developed
       • lots of mutants
       • gene function manipulation techniques

2. EARLY DEVELOPMENT

   • 1. eggs produced+fertilised in ovary
   • 2. travel down oviduct
     • 4-5 days
     • develop and divide here
     • ZONA PELLUCIDA: protective membrane preventing implantation here
   • 3. form BLASTOCYST
     • pre-implantation embryos can survive+develop in liquid media
   • 4. Hatch from zona pellucida
   • 5. implant in uterine wall
   • TOTIPOTENT until 8 cell

3. 8 Cell Stage: COMPACTION

   • MORULA
     • loose association of cells -> compact mulberry-like
   • 1. Cells POLARISE
   • 2. tight gap junctions form
   • 3. microvilli pull cells together
   • 4. impervious to external fluid
     • inside+outside environments
   • 5. CAVITATION: outer cells secrete vectorial fluid -> creates blastoceol

4. CELL FATE DECISIONS: segregation of...

   • TROPHECTODERM FROM ICM
     • Polarisation Model
       • conditioning (cytoplasmic determinants)
       • outer cells (TE) larger+polarised
         • TE-specifying cytoplasmic determinants APICALLY localised in polarised cells
       • SUPPORT: all inner cells generated from asymmetrical cleavage. (no definitive evidence)
     • "Inside-Out" Model
       • autonomous (cell signalling)
       • Compaction -> 2 microenvironments
       • SUPPORT: inner cells exposed to high cell density - this is associated with HIPPO signalling pathway
         • HIPPO down regulates TEAD4 + Cdx2 - TE determinants
   • PRIMITIVE ENDODERM FROM EPIBLAST LINEAGE
     • Stochastic Model
       • "salt+pepper"-like distribution of Epi + PrE determinants in early blastocyst
         • resolved by cell sorting and/or death
     • Positional Model
       • cavitation -> different microenvironments
         • cells facing blastocoel form PrE
     • "Time-outside/time-inside" Model
       • live-imaging and gene expression studies: origin determinant of which cells become PrE
         • 1st cells internalised (8-16 cell stage) -> EPI / bipotent precursor cells
         • cell internalised later (16-32) -> express GATA6 -> PrE

5. BLASTOCYST

   • TROPHECTODERM
     • -> chorion
     • Eomesodermin, Cdx2
   • EPIBLAST
     • -> embryo proper
     • nanog, Sox2, Stat3
     • PLURIPOTENT
   • PRIMITIVE ENDODERM
     • -> amnion
     • GATA6, GNCF, Sox17
   • ICM
     • Oct4
       • down-regs Eomesodermin+Cdx2
   • MUTUAL ANTAGONISTIC EXPRESSION
     • Oct4+Cdx2
       • cell can be throphectoderm OR ICM
     • Nanog+GATA6
       • can be epiblast or primitive endoderm

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