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Flashcards in Topic E5 Deck (14):

Define Germ Cell:

- cells that give rise to gametes during sexual reproduction


What are some features of germ cells?

- Initially pluripotent
- Reside in the gonads
- Pass genetic information onto the next generation
- undergo chromosomal recombination during meiosis and create haploid genomes
- highly sexually dimorphic


What is the origin of germ cells?

- Primordial germ cells emerge from the proximal posterior epiblast (PPE) and upregulate pluripotency genes and down regulate somatic genes to prevent them from differentiating
- These primordial germ cells become specialised but not sex determined before the reach the embryonic gonads
- Within the gonads sex determination occurs


How is the germ line specified in mammals vs non mammals?

Mammals: Regulative- germ line is induced by signalling factors such as TGF-B and BMPs

Non mammals: determinative- germ line is determined by inherited factors from mother


How does regulative specification of mammal germ line cells occur?

- Germ plasm factors are induced by signals sent from adjacent cells to cells in the PPE
- The most important of these signals BMP (bone morphogenetic protein, a member of TGF-B family of morphogens; which comes from the extraembryonic ectoderm
- BMP antagonists restrict BMP signalling to PPE; meaning that only cells in this specific region will be specified to become PGCs
- BMP signals from the extraembryonic endoderm activate -> Blimp1 gene + Prdm14 gene -> both of which activate pluripotency “germ cell” genes e.g. Sox2, Nanog, Nanos


How does migration of the PGCs to the gonads occur?

- The PGCs are specified in the PPE
- The PGCs express BLIMP1 and PDRM14
- The PGCs migrate via the hindgut to the gonads following chemoattracts secreted by the gonads (Sdf) which bind with the receptor Cxcr4 on the PGC
- Neigbouring cells release chemorepellents to further drive the PGCs towards the gonads


Is the sex of the PGCs determined when they arrive in the gonads?

- No


What two factors drive sex differentiation of the PGCs once they arrive in the gonads?

1. Inductive signals from the gonads (whether the gonad is an ovary or testis)

2. Sex chromosome complement of the PGC (XX vs. XY)


Describe the lifecycle of a female germ cell:

- Enter the ovary and undergo sex differentiation
- Proliferate
- Enter meiosis I and arrest and prophase I during embryonic development
- Remain in meiotic arrest and complete meiosis I at puberty
- Meiosis II completed during fertilisation


Describe the lifecycle of a male germ cell:

- Enter the ovary and undergo sex differentiation
- Proliferate
- Enter mitotic arrest during embryonic development
- Exit mitotic arrest during puberty and continue through meiosis I and meiosis II within semniferous tubules as part of sperm production


How is entry into meiosis regulated by retinoic acid signalling?

- Female germ cells enter meiosis within the embryonic embryo as the mesonephric kidney degrades vitamin A to retinoic acid and the retinoic acid binds to its receptor on the germ cells and activates the Str8 transcription factor which promotes DNA synthesis and entry into meiosis.

- Male germ cells do not to the same as although the mesonephros degrades Vitamin A to retinoic acid the retinoic acid is degraded by the Cyp26 enzyme which is highly active within the male gonad and degrades the retinoic acid before it can stimulate meiosis.
- Cyp26 is only deactivated within the male gonad at puberty


What is Epigenetic Reprogramming?

- When germ cells are specified within the proximal posterior epiblast the genomic imprints (e.g. methylation marks) are erased
- Once the germ cell migrates and enters the gonads and undergoes sex determination the epigeneic markers are re-established : this is epigenetic reprogramming


What is genomic imprinting?

- A process known as imprinting whereby some genes are epigenetically (without a change in the underlying DNA) switched off depending upon which parent (maternal vs. paternal) the gene came from.
- If a gene is silenced it is said to be imprinted


What is epigenetic modification?

- Changes in gene expression not due to changes in DNA sequence
- Instead the changes in gene expression can be due to:
1. Methylation of DNA (DNA methylated = gene inactive; DNA not methylated = gene active)
2. Modification of chromatin that packages the DNA (usually by methylation or acetylation of histone tails)
(Open chromatin = gene active; closed chromatin = gene inactive)