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Vertebrate
Mammalian Preimplantation Development
| Question | Answer |
|---|---|
| Stages of Mammalian Pre-Implantation Development? | Cleavages Compaction Lineage Specification Restriction of Potency Hatching and Implantation |
| What do different types of cleavages depend on? | Yolk content Yolk distribution |
| What type of cleavage occurs in mammals? | Holoblastic and Rotational |
| What does holoblastic mean? | Cleavage is equal and goes completely through the egg |
| Where does the first cleavage occur? | The Meridional plane |
| What does meridional plane mean? | Pole to pole |
| Where does the second division occur? | Meridional plane and Equitorial Plane |
| What does cleavage achieve? | It gives rise to equal size blastomeres |
| Each of the blastomeres at the 2 and 4 cell stages are....? | Totipotent |
| Where does fertilisation occur? | Infundibulum of the oviduct |
| What is the zona pellcucida and what is it composed of? | Covers the embryo and composed of glycoproteins |
| What does meiosis achieve in this process? | Generation of the polar body |
| What occurs at the 2 cell stage? | Foetal Transcription is initiated |
| What occurs at the 8 cell stage? | Compaction |
| What occurs at the 32 cell stage? | Cavitation |
| What day does the blastocyst hatch and implant into the uterine wall? | 4 days |
| Cleavage Definition? | Cell division occuring without any intervening growth; the embryo does not increase in size |
| What happens at the 4 cell stage? | The second polar body degenerates |
| What occurs during compaction? | Cell changes shape from loose cluster of spherical cells into a tightly packed mass of cells Gap junctions form between adjacent cells which seals the embryo from the external environment Outer cells become different from inner cells |
| What will the outer cells form? | The primitive trophectoderm |
| What will the inner cells form? | The inner cell mass cells |
| What happens at the uncompacted early 8 cell stage? | Membranes of individual blastomeres are delineated Golgi Body, Mitochondria, etc are distributed throughout the blastomere Cilia surround these cells allowing local cell contact |
| What happens at the compacted late 8 cell stage? | Basolateral differentiation forms a broader apical asurface and a narrower basal surface Redistribution of golgi and mitochondria to apical surface Tight junctions form between other cells Microvilli are over the apical surface |
| What role do the outer cells have in lineage specification? | Outer cells are polarised They have an apical and basal end Will become a trophectoderm Give rise to Trophoblast |
| What role does the ICM have in lineage specification? | Differentiated into the PE and EPI |
| What does the Epiblast give rise to? | The proper embryo |
| What does the fluid secreted by the inner cells do? | There is a unique directional transport of fluid from the external cells to the interior This gives rise to the blastocoelic cavity which pushed the cells of the inner cell mass towards one pole |
| What cellular changes occur when the blastocyst forms? | Epithelialization of the outer layer Establishment of polarity Vectorial fluid transport of fluid from the external cells into the internal cells Fluid creates this cavity ICM rapidly divides (no G2/G1) |
| First Lineage Specification - Trophectoderm vs ICM - Cellular Changes | A division plane orientated parallel to the axes of polarity gives rise to two outer polar daughter cells A division plane orientated perpendicular to the axes of polarity results in one outer cell and one inner apolar cell |
| What is important for TE/ICM segregation? | Cell position and Cell polarity |
| Which signalling pathways are important in TE/ICM segregation? | HIPPO and Ras/MAPK pathway |
| Trophectoderm Signalling | Hippo: expression of TE-specifying genes (Cdx2 and Gata3) in outer cells requires the transcription factor Tead4 and its coactivator Yap Ras/MAPK: activation of this pathway in TE cells resulting in expression of TE genes (Cdx2) |
| ICM Signalling | Increase in cell-cell contact results in activation of Hippo pathway - Yap is phosphorylated and Tead4 transcription is inhibited |
| Trophectoderm Transcriptional Network | Cdx2, Gata3, Eomes maintain the TE They induce each other and repress the ICM genes (Oct4 and Nanog) |
| ICM Transcriptional Network | Oct4, Nanog, Sox2, Sall4 are expressed in the ICM and repress TE specific genes (Cdx2) |
| Second Lineage Specification - EPI vs PE - Cellular Changes | Initiated by differential expression of Gata6 and Nanog Gata6 expressing cells form PE Nanog expressing cells form EPI Cell sorting from random to organised achieved by differential adhesion Positioning achieved by adding forces exerted by blastocoels |
| Second Lineage Specification - EPI vs PE - Signalling ICM | ICM express both growth factor Fgf4 and recepto Fgfr2 Fgfr2 activated Gat6 expression Gata6 antagonises Nanog |
| Second Lineage Specification - Signalling EPI | Nanog upregulated Fgf4 Loses Fgfr2 (required for Gta6 transcription) Nanog inhibits Gata6 Both lead to loss of Gata6 in EPI |
| Second Lineage Specification - Signalling PE | Gata6 expressed - retain Fgfr2 expression Fgfr2 can be activated by Fgf4 secreted by EPI Nanog inhibited by Fgfr2 and Gata6 Gata6 enhances own expression |
| Hatching and Implantation | Hatching from zona pellucida Proteases act on glycoprotein coat of ZP, forming a pore, allowing blastocyst to escape the ZP Blastocyst adhere to uterine wall |
| Applications of Preimplantation Development | Pre-natal diagnosis for inherited genetic disorders: haemophilia A, CF, muscular dystrophy Take one cell from the 8 cell stage and genotype it by PCR |