Biology Reference
In-Depth Information
this fidelity of transmission, PGC development encompasses extensive epigenetic repro-
gramming. The low cell numbers and relative inaccessibility of PGCs present a challenge
to those seeking mechanistic understanding of the crucial developmental and epige-
netic processes in this most fascinating of lineages. Here, we present an overview of PGC
development in the mouse and compare this with the limited information available for
other mammalian species. We believe that a comparative approach will be increasingly
important to uncover the extent to which mechanisms are conserved and reveal the
critical steps during PGC development in humans.
1. EMBRYOLOGY
In the early to mid-twentieth century, embryologists recognized
PGCs based on morphological characteristics such as their large size and
prominent nucleolus. The meticulous observations by
Witschi (1948)
meant
that human PGC development was among the best characterized of the
mammals. Witschi first discriminated PGCs in Carnegie stage (CS) 11
embryos (
embryonic day (E)24) in the extraembryonic yolk sac, close
to the junction with the allantois. In more advanced embryos of the same
CS, PGCs are found in the yolk sac as well as the developing hindgut
and by CS12 (
E26) all the PGCs reside in the hindgut. In CS13 embryos
(
E28), some PGCs are observed leaving the hindgut and entering the
region of the developing genital ridges. By CS16 (
E37), all of the PGCs
have left the gut and its mesentery and can be found in the genital ridges.
Witschi noted that the PGCs in the hindgut form pseudopodia and “show
signs of locomotor activity.” He suggested that migration at this stage
may be due to “active movements” of individual cells, observations con-
firmed in the mouse over 50 years later (
Molyneaux, Stallock, Schaible,
& Wylie, 2001
). Witschi noted that throughout the migratory period, from
yolk sac to genital ridge, PGCs increase in number. He also concluded
that “No facts and no convincing theoretical arguments in favor of second-
ary germ-cell formation during the period covered by this investigation
were found. The germ cells are strictly specific and do not change into
somatic elements.” Sexual differentiation of the gonadal somatic cells
begins at the beginning of the 7th week followed by the expression of
sex determination genes
Sry
and
Sox9
(
Hanley et al., 2000
). Thereafter,
germ cells are referred to as gonocytes. In female, gonocytes enter meiosis
at the 10th week (
Gondos, Westergaard, & Byskov, 1986
), whereas male
germ cells do not undergo meiosis until after puberty.
