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Vertebrate

Mammalian Preimplantation Development

QuestionAnswer
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
Created by: beccaaxo1
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