The saga of germ line

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The Saga of Germ line

Saga of Germ lineTwo step process;

Primordial germ cells (PGCs) are determined in a specific location in the embryo

PGCs migrate to the gonad and become the progenitor population for eggs and spermGerm cell determination in nematodesPascaris acquorum- 2 chromosomes per haploid cell- equatorial cleavage division

Uniqueness: Chromosome diminution* In this phenomenon, only a portion of original chromosomes survives and numerous genes are lost.

Germ cell determination in nematodes

4Germ cell determination in insectsDrosophilaPole Cells (group of PGCs) at the posterior pole of the cellularizing blastoderm

Components of Pole plasm in InsectsmRNA of the gcl genesOskar- cause the to form germ cellsNanos- essential for germ cell formationVasa- RNA-binding proteinsMitochondrial ribosomal RNA (mtRNA)- restores the ability of embryos to form pole cellsPolar granule component (pgc)- function remains unknownGerm cell determination in amphibians

Germ plasm of unfertilized eggs consist of tiny islands that appear to be tethered to the yolk mass near the vegetal cortex.

Germ plasm islands move with the vegetal yolk mass and begin fusing together and migrating to the vegetal pole.

Germ cell migration in amphibiansGerm plasm collects around the vegetal pole in the zygote.

PGCs become concentrated in the posterior region of the larval gut, and as abdominal cavity forms.

Xenopus PGCs move by extruding a single filopodium and then streaming their yolky cytoplasm into that filopodium while retracting their tailAnd PGCs migrate along he dorsal mesentery and then along the abdominal wall and into the genital ridges until they reach the developing gonad.The pathway for germ cell migration in frogs appears to be composed of an fibronectin-containing extracellular matrix.9

Germ cell migration in mammalsPGCs reside in the epiblast of gastrulating embryo.

FIBRONECTIN- an important substrate for PGC migration and germ cells that lack the integrin receptor.

-Using monoclonal antibodies (recognize cell surface differences between the PGCs and surrounding cells)10Germ cell migration in birds and reptiles

PGCs are derived from epiblast cells that migrate from the central region of area pellucida to crescent-shaped zone in hypoblast called GERMINAL CRESCENT.PGCs migrate to the gonads through blood stream.PGCs of the germinal crescent enter the blood vessel by DIAPEDESIS.When blood vessels form in the germinal cresecent, the PGCs enter those vessels and carried by the circulation to the region where the hindgut is forming and exit from circulation, it associates with mesentery and migrate into genital ridges.DIAPEDESIS- type of movement common to lymphocyte and macrophages that enables cells to squeeze between endothelial cells of small blood vessels.

11Germ cell migration in Drosophila

PGCs move from the posterior pole to the gonads1st step- 30-40 pole cells are displaced into the posterior midgut by the movements of gastrulation2nd step- gut endoderm triggers active amoeboid movement in the PGCs, which travel through he bind end of the posterior midgut, migrating into the visceral mesoderm3rd step- PGCs split into 2 groups, each of will become associated with developing gonad primordium.4th step- PGCs migrate to gonads, which are derived from the bilateral mesoderm

This step involves the attraction and repulsion that involves the wunen gene (directs the migration of PGCs from the endoderm into the mesoderm) And Columbus gene (necessary for the gonad to attract the PGCs.12Big Decisions: Mitosis or Meiosis? Sperm or Egg?In many species, the germ cells migrating into gonad are bipotential and can differentiate into either sperm or ova, depending on their gonadal environment.In Caenorhabditis elegans 2 decisions that presumptive germ cells have to make:Whether to enter meiosis or to remain a mitotically dividing stem cell.Whether to become an egg cell or sperm cell.

Meiosis or MitosisThe mitotic/meiotic decisions is controlled by a single non-dividing cell at the end of each gonad, the DISTAL TIP CELL.Germ cell precursors near this distal tip cell divide mitotically, forming pool or germ cells, but as these cells get farther away from the distal tip cell, they enter meiosis.If the DTC is destroyed, all the germ cells enter meiosis and if it is placed in different location, germ line stem cells are generated near to its position.

Lag-2 protein- maintains germ cells in mitosis - inhibits their meiotic differentiationThe DTC extend long filaments that touch the distal germ cells, the extensions contain Lag- 2 protein in their cell membrane.14SPERM or OVAAfter germ cells begin their meiotic divisions, they still must become either sperm or egg.In each ovatestis: most proximal germ cells produce sperm while most distal (near tip) become egg.MEANING: germ cells entering meiosis early become sperm while those entering meiosis later become eggs.

During early development, the fem genes (fem-3) are critical for sperm cells specification. fem genes activates the fog genesFUNCTIONS of fog genes:- the products activate the genes invoved in transforming the germ cell into sperm cell- inhibit those genes that would otherwise direct the germ cells to initiate oogenesisThe laboratories of Hodgkin (1985) and Kimble (Kimble et al. 1986) have isolated several genes needed for germ cell pathway selection, but the switchappears to involve the activity or inactivity of fem-3 mRNA.- As long as FEM proteins are made in germ cells, sperm cells are produced. LOSS of FUNCTION of FEM GENES CONVERTS NEMATODES INTO FEMALE.

16SPERMATOGENESIS and OOGENESISWhile the reductive divisions of meiosis are conserved in every eukaryotic kingdom of life, the regulation of meiosis in mammals differs dramatically between males and females.

The initiation of spermatogenesis during puberty is regulated by the synthesis of BMP8B by spermatogonia.

After reaching the gonad, PGCs divide to form type A1 spermatogonia (smaller than PGCs and with ovoid nucleus).

When BMP8B reaches a critical concentration, germ cells begin to differentiate. The differentiating cells produce high levels of BMP8B, which can further stimulate their differentiation.19During spermatogonial divisions, cytokinesis is not complete. Cells form a SYNCYTIUM whereby each cell communicates with the other via cytoplasmic bridges.

The spermatids that are connected in this manner have haploid nuclei, but are functionally diploid, since a gene product made in one cell can readily diffuse into the cytoplasm of its neighbors.

OOGENESISOogenesis the differentiation of the ovum differs from spermatogenesis in several ways. Whereas the gamete formed by spermatogenesis is essentially a motile nucleus, the gamete formed by oogenesis contains all the materials needed to initiate and maintain metabolism and development.The mechanisms of oogenesis vary among species more than those of spermatogenesis. This difference should not be surprising, since patterns ofreproduction vary so greatly among species.21OOGENESIS IN MAMMALSMost oogonia die during this period, while the remaining oogonia enter the first meiotic division.Primary oocytes, progress through the first meiotic prophase until the diplotene stage, at which point they are maintained until puberty.Oogenic meiosis also differs from spermatogenic meiosis in its placement of the metaphase plate.The smaller cell is called the first polar body, and the larger cell is referred to as the secondary oocyte.In the human embryo, the thousand or so oogonia divide rapidly from the second to the seventh month of gestation to form roughly 7 million germ cells (Figure 19.19). After the seventh month of embryonic development, however, the number of germ cells drops precipitously.22Snapshot Summary: The Germ Line1. The precursors of the gametes the sperm and eggs are the primordial germ cells. They form outside the gonads and migrate into the gonads during development.2. In many species, a distinctive germ plasm exists. It often contains the Oskar, Vasa, and Nanos proteins or the mRNAs encoding them.3. In Drosophila, the germ plasm becomes localized in the posterior of the embryo and forms pole cells, the precursors of the gametes. In frogs, the germ plasm originates in the vegetal portion of the oocyte.4. In amphibians, the germ cells migrate on fibronectin matrices from the posterior larval gut to the gonads. In mammals, a similar migration is seen, and fibronectin pathways may also be used.5. In birds, the germ plasm is first seen in the germinal crescent. The germ cells migrate through the blood, then leave the blood vessels and migrate into the genital ridges.6. Germ cell migration in Drosophila occurs in several steps involving passive translocation, repulsion from the endoderm, and attraction to the gonads.7. Before meiosis, the DNA is replicated and remains bound at the kinetochore. Homologous chromosomes are connected through the synaptonemal complex. The configuration of the four chromatids is called a tetrad.8. The first division of meiosis separates the homologous chromosomes. The second division of meiosis splits the kinetochore and separates the chromatids.9. The meiosis/mitosis decision in nematodes is regulated by the Delta proteins, which bind to the Notch proteins on the PGCs. The decision for a germ cell to become either a sperm or an egg is regulated at the level of translation of the fem-3 message.10. Spermatogenic meiosis in mammals is characterized by the production of four gametes per meiosis and by the absence of meiotic arrest. Oogenic meiosis is characterized by the production of one gamete per meiosis and by an arrest at first meiotic prophase to allow the egg to grow.11. In some species, meiosis is modified such that a dipl