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Flashcards in lecture 20: germ cells Deck (20):

What were early observations on sperm and eggs?

  • entire body in the head of sperm etc 
  • really weird ideas in 17th C
  • whole person inside sperm - person inside the sperm of the person 
  • preformist theory
  • ovust stream thought the being existed inside the egg 
  • neoformist - organs and cells developed slowly over time 


What are germ cells?

  • the gametes (eggs and sperm) 
  • primordial germ cells (PGCs) are precursors to the gametes
  • transmit genetic information from one generation to the next 
  • basically the reason why we are here 


What is the life cycle of germ cells?

  • specification
    • up-regulation of pluripotency genes 
    • down-regulation of somatic genes 
    • proliferation (mitosis) 
  • migration to the genital ridges (future gonads)
    • proliferation (mitosis) 
    • erasure of epigenetic imprints 
  • sexual differentiation (mitotic arrest or meiosis)
    • epigenetic reprogramming 
  • gametogenesis (ova or spermatozoa) 
  • fertilisation 


What are mechanisms of PGC specification?

  • determinative (preformistic) 
    • depends on inheritance of germ plasm
  • regulative (epigenetic)
    • germ cell fate specified by cell-cell interactions and signalling 


What is determinative (preformistic) PGC specification?

  • insects, nematodes, fish, birds & frogs
  • inheritance of germ plasm – cytoplasm rich in specialised RNA binding proteins, RNA and mitochondria 
  • germ plasm contains inhibitors of transcription and translation 
  • germ cells specified very early in development 
  • e.g. vasa positive cells in zebra fish 


What is regulative PGC specification?

  • mammals, urodeles (e.g. salamanders)
  • depends on signals from adjacent cell populations 
  • ancestral form of germ cell specification? 


How do germ cells differ from somatic cells in their cell lineages?

  • need to upregulate pluripotent genes in germ cells, downregulate somatic genes 
  • in somatic cells → upregulate somatic genes 


What are key processes of PGC specification?

  • increased expression of pluripotency genes e.g. Sox2 and Nanoh 
    • Prdm1 
  • decreased expression of somatic mesodermal genes e.g. Hox genes, Brachyury 
    • Prdm1
  • increased expression of germ cell-specific genes e.g. stella, nanos3
    • prdm14 
  • extensive epigenetic remodelling 
    • prdm14 


What is germ cell proliferation?

  • E6.25 mouse: ~6 PGCs
  • by E13.5, ~25,000 germ cells
  • proliferation requires numerous growth factors and proteins 
  • autocrine or paracrine signals (SCF/c-kit, FGFs, LIF) 


What is PGC migration?

  • migratory route guided by ECM 
  • chemoattractive and repulsive signals are also involved 


What is PGC migration in a wallaby foetus?

  • wallaby foetus about 23 days into a 27 day 
  • migrate from the gut, through dorsal mesentery into the gonads, near mesonephros 
  • migration is induced by factors produced in the tissues of the foetus and corresponding factors or receptors in the germ cells, and the extracellular matrix 
  • series of signals that is both chemoattractive and chemorepulsive 
  • PGCs tend to migrate in clumps 
  • ECM has a big role:
    • laminin, fibronectin etc
    • changes with time 
  • e.g. body cells might express Stem Cell Factor, germ cells might express the receptor ckit, SDF1 by germ cells, receptor in body tissues 
  • quite regulated 
  • overlap between signals that encourage proliferation and stop cell death   


What is germ cell sexual differentiation?

  • first step is meiosis 
  • in mice: at E13.5-14.5 female germ cells enter meiosis, males enter mitotic arrest 
  • germ cell differentiation depends on the somatic environment initially, then on the chromosomal component of the germ cells 


What is meiosis?

  • unique to germ cells
  • exchange of genetic material 
  • production of haploid gametes 


What is control of entry into meiosis?

  • VitA (mesonephros) → RA → RA (ovary) → Stra8 → meiosis 
  • in testis Cyp26b1 inhibits RA meaning no Stra8 and no meiosis 


What is inequivalence of information from eggs and sperm?

  • e.g. horse x donkey 
    • mare x jack → mule 
    • jenny x stallion → hinny 
  • gametes carry the same genetic information but some of it is differentially modified between the sexes (= epigenetic modification) 


What are epigenetic modifications?

  • heritable changes to DNA or chromatin structure but not to DNA sequence 


What are mechanisms of epigenetic modifications?

  • DNA modifications e.g. methyl groups on CpG islands 
  • histone modifications
    • active/open chromatin 
    • inactive/condensed chromatin 
  • developmental signals establish specific pattern on → dna binding proteins → chromatin structure and DNA methylation 
  • DNA methylation help establush and maintain → chromatin structure → DNA binding proteins
  • DNA methylation influences binding of → DNA binding proteins 
  • main epigenetic modification in germ cells is DNA methylation 
  • genomic imprinting – expression of a gene in a parent-of origin specific manner 
  • e.g. 
    • female germ cells: 17 maternally methylated genes with an average level of ~40% DNA methylation 
    • male germ cells: 4 paternally methylated genes with an average level of ~89% DNA methylation  


What is the epigenetic control of germ cell development?

  • epigenetic reprogramming of germ cells is required for: 
    • correct gene expression 
    • X chromosome inactivation/reactivation 
    • progression of meiosis 
    • gametogenesis 


What is modification of imprint status?

  • main epigenetic modification in PGCs is DNA methylation 
  • epigentic erasure of imprinted loci before and as germ cells arrive at genital ridge 
  • new imprint status established after sexual differentiation:
    • females: after birth, during prophase I 
    • males: during mitotic arrest 
  • removal of DNA methylation by TET (ten-eleven translocation) proteins 
  • re-establishment of DNA methylation by de novo DNA methyltransferases (DNMTs) 


What is epigenetic control of gametogenesis?

  • spermatids: histones replaced by protamines 
  • oocytes contribute factors for post-fertilisation reprogramming (transcription factors and epigenetic modifiers)