A note on the origin and migration of germ cells in vertebrates.

1. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
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Origin and Migration of Germ Cells in
Vertebrates
In vertebrates, there is an established germ line that separates from the somatic cells
early in development; their germ cells often do not arise within the gonad itself. Rather,
the primordial germ cells (PGCs) arise elsewhere and migrate into the developing
gonads (PGCs give rise to the germ cells). The first step in gametogenesis involves
forming the PGCs and getting them into the genital ridge as the gonad is forming.
“The primordial germ cells in an embryo develop into stem cells that in an adult
generate the reproductive gametes (sperm or eggs), i.e. PGCs give rise to germ
cells/gametes.”
All gametes arise from primordial germ cells. The primordial germ cells are either
specified autonomously by cytoplasmic determinants in the egg, or due to the
interactions with neighboring cells.
“Germ plasm is the term used for all of the cytoplasmic components (proteins and
mRNAs), that bring about the determination of the primordial germ cells autonomously.”
Germ Cell Determination In Vertebrates:
Germ cell determination in various vertebrates takes place as follows:
 Frogs: The germ plasm of amphibians consists of germinal granules and a matrix
around them; it is present at the vegetal pole of the zygote.
 Zebrafish: In zebrafish, the germ plasm forms a dense structure characterized by
polar granules, mitochondria, and concentrated mRNAs. Later on, four clusters of
PGCs are formed.
 Mammals: In mammals, there is no obvious germ plasm. Rather, germ cells are
induced in the embryo. In mice, the germ cells form at the posterior region of the

2. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
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epiblast. The cells that become the PGCs in mice are not different from the other
cells of the epiblast and contain no specific germ plasm. Rather, the posterior
epiblast cells are induced by the extra-embryonic tissue to become PGCs.
Inert Genome Hypothesis:
“According to Inert Genome Hypothesis, the cells become germ cells because they are
forbidden to become any other type of cell.” For example, in mice, the germ cells
undergo extensive chromatin modification, causing them to become transcriptionally
inert at embryonic day 8.5.
Germ Cell Migration In Vertebrates:
Germ cell migration in vertebrates can be understood from the examples of zebrafish,
frogs, mammals, birds, and reptiles.
1. Zebrafish:
Zebrafish PGCs (primordial germ cells) arrive at the gonads via chemoattraction
(attracted by chemical agents). Initially, PGCs are in four clusters, but by the end of the
first day of development (at the 1-somite stage), the PGCs are found in two clusters
along the border of the trunk mesoderm. From there, they migrate posteriorly into the
developing gonad. In zebrafish, the primordial germ cells follow a gradient of the Sdf1
protein that is secreted by the developing gonad. The receptor for this protein is the
CXCR4 protein on the PGC surface. Loss of either CXCR4 from the PGCs or Sdf1 from
the somatic cells results in random migration of the zebrafish primordial germ cells.
2. Frogs:
The germ plasm (genetic material of germ cells) of anuran amphibians (frogs and toads)
collects around the vegetal pole in the zygote. During cleavage, the germ plasm is
brought upward through the yolky cytoplasm. Periodic contractions of the vegetal cell
surface push it along the cleavage furrows of the newly formed blastomeres. Germ

3. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
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plasm eventually becomes associated with the endodermal cells lining the floor of the
blastocoel.
Figure: Migration of Xenopus germ plasm. (A-C) Changes in the position of the germ
plasm (color) in an early frog embryo. (A) The germ plasm is located near the vegetal
pole of the uncleaved egg, (B) it moves along the cleavage furrow (C) until it becomes
localized at the floor of the blastocoel.
The PGCs become concentrated in the posterior region of the larval gut, and as the
abdominal cavity forms, they migrate along the dorsal side of the gut, into the genital
ridges. They migrate up this tissue until they reach the developing gonads.
Xenopus (specie of frog) PGCs move via a single filopodium (thin cytoplasmic
projections, involved in cell migration). Both the PGCs and the extracellular matrix over
which they migrate are oriented in the direction of the migration. As they migrate,
Xenopus PGCs divide about three times, so that approximately 30 PGCs will colonize
the gonads. These cells will divide to form the germ cells. The mechanism by which the
Xenopus PGCs are directed to the gonad involves a CXCR4 protein on the PGC
responding to an Sdf1 protein along the migration path.

4. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
pg. 4
3. Birds & Reptiles:
In birds and reptiles, the primordial germ cells (PGCs) are derived from epiblast cells
(epiblast gives rise to ectoderm, endoderm, and mesoderm) that migrate from the
central region of the area pellucida (the translucent central area of the blastoderm of
birds and reptiles within which the embryo develops) to a crescent-shaped zone, the
germinal crescent (the PGCs multiply here). The PGCs of birds and reptiles migrate to
the gonads primarily through the bloodstream. When blood vessels form in the germinal
crescent, the PGCs enter those vessels and are carried by the circulation to the
intermediate mesoderm. Here they leave the circulation and migrate into the genital
ridges. Chemotaxis is also involved in this migration, the molecules that chick PGCs use
for chemotaxis may be the same Sdf1/CXCR4 chemotactic system as used by
zebrafish.
4. Mammals:
Mammalian PGCs form in the posterior epiblast (epiblast gives rise to ectoderm,
endoderm, and mesoderm) and migrate directly into the endoderm from the posterior
region of the primitive streak (present on the dorsal side, gives rise to notochord). At the
9th embryonic day, the PGCs exit the gut. The next day, PGCs migrate into the genital
ridges. By embryonic day 11.5, the PGCs enter the developing gonads. During this
journey, their population has increased from 10-100 cells to 2500-5000 PGCs (present
in the gonads by day 12).