Lecture 3: Sex Determination and Gametogenesis

13.1.2026

Why have dedicated PGCs?

• Protect heritable information (genome)

• Fewer cell divisions=less chance of aneuploidy

• Less “dirty work” (metabolic work can lead to oxidative stress)

• Liberates the soma to modify more

Connection between PGC development and speciation

Earlier PGC development correlates with species number (In vertebrates)

Sex determination

The process that commits individuals to a specific reproductive role

Primary sex traits

Anatomical and physiological traits that contribute directly to reproduction

Secondary sex traits

Anatomical and physiological traits that increase reproductive success (but do not directly contribute to reproduction)

Primary sex determination

Differentiation of gonads

Secondary sex determination

Downstream changes, often based on gonads

• Qualitative, not binary

• Variation in timing and magnitude

• Traits can vary between tissues

• Outcomes of intersecting processes (hormones, receptors, developmental timing, environment)

Mechanisms of primary sex determination

• Derived, has evolved multiple times

• Evolved when there is an advantage to having individuals with different reproductive roles

Genetic/ chromosomal sex determination

Sperm come in two forms, determining sex

Sex determination in mammals

X and Y, Y denotes maleness

Primary sex determination in mammals

Occurs after the pharangula stage of embryogenesis

In XY embryos, Sertoli cells differentiate → producing signals → testes and male genitalia develop =”Active”

In XX embryos granulosa cells develop instead → ovaries and female genitalia develop = “Default”

Evidence for Y-centric sex determination in mammals

Klinefelter Syndrome: XXY = still male

Turner Syndrome: XO=Still female

XX “males” = part of Y chromosome translocated to X chromosome, develop male phenotype

XY “females” = part of Y chromosome missing, develop female phenotype

SRY

Found on short arm of Y chromosome

Activates Sox9

Sox9

Maintains its own expression through a positive feedback loop

Turns on Fgf9

Fgf9

Inhibits Wnt4, which would otherwise promote female development

Bistable switch

Characterization of sex determination

A gene regulatory network, commits a cell to one of two mutually exclusive states

Male and female phenotypes = alternative active states

Drosophila sex determination

• X-centric

• Cell-autonomous

• XO=male, XXY=female

• X:A ratio matters

• More X : increased Sxl expression

X:A ratios in Drosophila

XX2A=female

XY or XO2A = male

XXX2A=metafemale

XX3A = intersex

X,3A=metamale

Sxl

Sex determination gene in Drosophila

Reinforces its own development, activates female development

Grasshopper sex determination

No Y chromosome, XO=male

Bird sex determination

ZZ=male

ZW=female

Z gene dose determines sex

Haplo-diploid system

Honeybee sex determination

Males = haploid

Females = diploid

Environmental sex determination

Ex: in sea turtles

Can be temperature- based

or based on social clues (sequential hermaphroditism)