DEV2011 Lecture Notes - Lecture 8: Prdm1, Yolk Sac, Somatic Cell
25 May 2018
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Lecture 8 – Germ Lineage and Sex Determination
• Specification, proliferation, maintenance and differentiation of primordial
germ cells have profound bearing on number and function of future germ cells
• Muticellular eukaryotes made of two cell types: somatic and germ cells
Germ Cells
• Germ cells produce gametes – only cells that can undergo meiosis as well as
mitosis
o Cells sometimes immortal because they form link between generations
• Germ cells are biological cells that give rise to gametes of an organism that
reproduces sexually
• Beginning: separating germline from somatic lineages is one of the first
decisions made by the embryo
• Germ line: want to keep cells separate
o Need germ cells to retain pluripotent state while ectoderm and
mesoderm cells are developing
• Zygote → blastula → gastrula:
o Within gastrula: germ layers (ectoderm, mesoderm, endoderm) + germ
cells
• Primordial germ cells (PGCs) protected from all signals that are driving
differentiation (somatic cell differentiation) in gastrulating layers via
combination of transcriptional and translational suppression
• Majority of germ cell development takes place in embryo
• Germ cells move from midline of embryo into gonads after 16-20 hours
Primordial Germ Cell Journey
1. Specification
• Around 6 cells in mouse embryo express the Blimp1 gene (E5.5-6.5)
• Lineage is specified
• Embryonic stem cell approaches – allowing period of development to
be investigated
2. Commitment
• After proliferation – subset of Blimp1 positive cells express Stella –
commit to germ line
3. Migration
• PGCs undergo both passive and active migration to gonads
o Active migration: proteins expressed on surface of cells →
follow pathway
• Extensive proliferation occurs during migration
• Gonads
• Colonise 11.5 dpc
• During 4th week of human gestation, PGCs migrate from yolk sac and
into developing embryo
• Extensive proliferation occurs during the journey
4. Colonisation
• PGCs colonise the gonads and undergo sex determination (week 6-8 of
gestation)
o Oogonia enter meiosis but stop at prophase I of meiosis I (at
week 12) until puberty
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o Females germ cells: PGCs differentiate into oogonia
▪ Gonads stay in abdomen
o Males: PGCs form gonocytes. Gonocyte undergo mitosis-arrest
mitosis and don’t enter meiosis until puberty
▪ Followed by intermediate spermatogonia and
prespermatogonia
Sex Determination – Importance of SRY
• SRY – located on Y chromosome
• SRY switches on – cascade of genes responsible for male gonadal
development
o Drives genital gonad → testis
▪ DHT → produces testosterone: supports male external genitalia
▪ Causes cells in testis to produce AMH (anti-mullerian
hormone)
• Absence of SRY:
o Turn into ovary
Sex Determination in Mammals is a Process
• Genetic, gametic, chromosomal sex → gonadal sex → phenotypic sex:
internal and external (same tissue but plastoceme moulded differently)→
behaviour and metabolic sex
• When Sex determination goes wrong
o Chromosomal aberrations
▪ X and Y genotype but female in appearance
▪ E.g. Swyer syndrome, 46 XY
▪ Phenotypically females (External)
▪ Streak ovaries (increased likelihood of cancer)
▪ Missing SRY gene
▪ No post-pubertal development of 2˚ sex characteristics (lack of
hormone production)
▪ No germ cells of own
• May become pregnant with donated egg/embryo
o Affects gonadal development and development of secondary sexual
characteristics → physical development
Disrupted Development – tumors of male germline
• Testicular cancer: cancers of germ cells of testes → increase in rate
• Disease that occurs in embryogenesis
• Specification, migration, colonisation → germ cells arrest in differentiation
and transformation → CIS tubules in testes → progresses to malignancy →
seminoma → non-seminoma
Meiosis
• Oogenesis and spermatogenesis many features in common
o Extensive morphological differentiation
o Incapacity of surviving for very long if fertilizaiton does not occur
find more resources at oneclass.com
find more resources at oneclass.com
