Topic E5

Question 1

Define Germ Cell:

Answer 1

• cells that give rise to gametes during sexual reproduction

Question 2

What are some features of germ cells?

Answer 2

• 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

Question 3

What is the origin of germ cells?

Answer 3

• 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

Question 4

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

Answer 4

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

Question 5

How does regulative specification of mammal germ line cells occur?

Answer 5

• 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

Question 6

How does migration of the PGCs to the gonads occur?

Answer 6

• 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

Question 7

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

Answer 7

• No

Question 8

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

Answer 8

1. Inductive signals from the gonads (whether the gonad is an ovary or testis)
2. Sex chromosome complement of the PGC (XX vs. XY)

Question 9

Describe the lifecycle of a female germ cell:

Answer 9

• 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

Question 10

Describe the lifecycle of a male germ cell:

Answer 10

• 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

Question 11

How is entry into meiosis regulated by retinoic acid signalling?

Answer 11

• 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

Question 12

What is Epigenetic Reprogramming?

Answer 12

• 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

Question 13

What is genomic imprinting?

Answer 13

• 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

Question 14

What is epigenetic modification?

Answer 14

• 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)