Sex Determination

Sex Determination
 Sex determination is a question of how mammals develop into males or females
 Primordial germ cells start outside of “embryo proper” in the extraembryonic
material (yolk sac)
o Germ cells proliferate and migrate to eventually form one type of gonad
o Primordial germ cells can be identified by staining with alkaline phosphatase
 Primordial germ cells are present in humans around three weeks post
fertilisation
 Can be found at E6 in mice
o During migration primordial germ cells move from the yolk sac to the hindgut,
to the dorsal mesentry to the gonadal ridges
 The cells undergo mitosis whilst migrating
 Initially, they migrate passively, then it becomes active
 Gonads are already populated by somatic cells from the mesonephros
o Embryo has two genital ridges which is where the ovaries or testis form
o Migrating primordial germ cells split into two groups to go to the different
genital ridges
 Gives a left and right gonad




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 Sex determination in relation to genes is well known
o 3 particular genes are necessary and have a big impact on cell migration and
proliferation:
 TGFβ (transforming growth factor beta)
 Kit ligand (also called SCF/ steel gene)
 bFGF (basic fibroblast growth factor)
 The genital ridge is already populated by somatic cells
o When germ cells reach the area, they become surrounded by somatic cells

, o Germ cells change from being called primordial germ cells to
prespermatogonia/prospermatogonia in males and oogonia in females
 Use of mouse knockouts has given us a lot of knowledge about gene determination
of sex
o In EMX2 knockout, no gonads form
o In SF1 knockout, gonads start to form and then die
o In WT1 knockout, kidneys and gonads develop, then kidney development stops
(along with somatic cells that would move to the genital ridge), then gonad
development stops
 From the time that germ cells first reach the genital ridge, until a proper genital is
formed, the area is known as an indifferent gonad
o The indifferent gonad has the ability to become either type of gonad
 Known as bipotential
 Either one organ or group of cells can develop in two ways
 Happens in mammals
 Or two organs or cell types develop, then one dies
 Happens in some other species
 The secondary sex characteristics you develop depend on whether you develop testis
or ovaries
o Alfred Jost, in the 1940s, removed the testis or ovaries from rabbits
 All rabbits developed as female
 Showed that female is the default state
 Developing as a male is an active process
o Germ cells themselves are not required for the process
 Blocking kit ligand (therefore stopping germ cells reaching the gonads)
doesn’t stop the development of secondary sex characteristics
 Means that somatic cells are sufficient for this programming
 In development, embryos have two sets of ducts




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