week 12 Flashcards
what is gametogenesis?
the formation of germ cells
gametogenesis includes which 5 processes?
the formation of the germ plasm and the determination of the PGCs
the migration of the PGCs into the developing gonads
the process of meiosis and the modifications of the PGCs into the developing gonads
the process of meiosis and the modifications of meiosis for forming sperm and egg
the differentiation of the sperm and egg
the hormonal control of gamete maturation and ovulation
there are 2 methods of PGC determination
PGCs can be specified by cytoplasmic determinants in the egg: the germ plasm
PGCs can be specified by interactions among neighbouring cells
Germ cell determination by cytoplasmic determinants in nematodes (worms).
What happens to the chromosomes in nematodes?
chromosomes fragment into dozens of pieces in somatic cells. the germ plasm prevents fragmentation
In the nematode c.elegans the germ line precursor cell is the ____
P4 blastomere
P-granules become localised to the P4 blastomere. What are these?
these are ribonucleoprotein complexes that specify the germ cells
what do the P-granule proteins contain?
several transcriptional inhibitors and RNA binding proteins
why dont germ line cells turn into somatic cells?
expression of somatic genes is inhibited in the P4 blastomere preventing the cell to differentiate into a somatic cell
In Drosophila PGCs form how?
as a group of pole cells at the posterior pole of the blastoderm. Nuclei migrate to the posterior area and become surrounded by the pole plasm
The __ ___ specifies the germ cells and inhibits somatic gene expression in these cells in Drosophila
pole plasm
Drosophila - the mRNA of the maternal gene germ cell-less (gcl) is localised to the posterior pole. What is the protein?
the protein is a component of the pole plasm and is essential for pole cell production
what are required in drosophila for localising mRNAs and proteins to the posterior pole?
posterior group determinants
what is Oskar and Nanos?
Oskar functions by localising proteins and mRNAs necessary for germ cell formation.
Ectopic Oskar localisation results in ectopic germ cells.
Nanos is localised by Oskar.
Nanos prevents the pole cells from developing into somatic cells
In the unfertilised frog egg the germ plasm consists of what?
several islands bound to the yolk. these islands fuse together and migrate to the vegetal pole after fertilisation.
What is the function of the germ plasm?
inhibition of transcription and translation of somatic genes
induction of germ cell development
How is the germ cell determined in mammals?
no germ plasm
BMP signals from the extra embryonic ectoderm induce neighbouring embryonic cells to become germ cell precursors. During gastrulation the germ cell precursors become located in the posterior part
broadly how do germ cells migrate in drosophila?
germ cells form as a group of pole cells. Pole cells attach to endoderm (posterior midgut rudiment) and are displaced into the pmg by the gastrulation movements (passive movement)
Germ cell migration in Drosophila. :
Gut ____ triggers the pole cells to migrate (active movement) through the blind end of the ___
Pole cells attach to mesoderm. The ___ protein directs migration from endoderm to mesoderm by ____.
Pole cells align with gonadal mesoderm. The proteins ___ and ___ (produced by the gonads) attract the pole cells
Pole cells and gonad precursor cells are divided into two streams. The ____ protein is involved in the separation
The ____ coalesce around the germ cells, the germ cells can now divide and mature into gametes
endoderm pmg Wunen Repulsion Columbus Hedgehog Wunen gonads
Gonadal maturation occurs during ____
metamorphosis
What happens to the PGCs at metamorphosis?
the PGCs in the anterior region of the gonad become stem cells. Asymmetric division occurs - stem cell + cytoblast
How is the egg chamber formed?
The cytoblasts are interconnected by the ring canals (cytoplasmic bridges). One of these cells becomes the oocyte (egg), the remaining 15 cells become nurse cells. The nurse cells produce RNAs and proteins that are transported into the egg
How does the germ cell migrate in the zebra fish?
the germ plasm accumulates along the cleavage planes during the first two divisions. There are four clusters of germ cells in the early zebrafish embryo. The PGCs follow a gradient of the Sdf1 protein. Sdf1 is secreted by the developing gonads and the PGCs express the sdf1 receptor CXCR4
Germ cell migration in mammals.
PGCs move from the posterior region of the primitive streak into the ______.
PGCs then exit the gut and migrate towards the genital ridge (_____)
migration occurs along the __ and probably involves soluble proteins like Sdf1 in the zebrafish.
hindgut (endoderm)
gonade primordium
ECM
In mammals the PGCs proliferate during migration (from 10 to 5000). Proliferation depends on what?
FGF7 and the stem cell factor SCF
The maturation of germ cells occurs when?
the germ cells reduce their chromosomes from the diploid to the haploid condition
meiosis differs from mitosis in that? (2)
homologous chromosomes pair together and combine genetic material
meiotic cells undergo two cell divisions without an intervening period of DNA replication
In higher eukaryotes all cells are diploid except?
the egg and sperm are haploid
Spermatogenesis in mammals
PGCs become incorporated in to the sex chords in the testis. The sex cords then hollow out and form the seminiferous tubules. The epithelium of the tubules differentiates into the sertoli cells
what do the sertoli cells do?
protect and nourish
the initiation of spermatogenesis occurs at puberty and depends on high concentrations of ______ in the PGCs
BMP8b
What is the transition between spermatogonia and spermatocytes induced by? and where is this secreted?
GDNF
sertoli cells
As germ cells mature they progress where?
towards the lumen of the seminiferous tubule
Why does oogenesis differ from spermatogenesis?
the sperm are essentially motile nuclei, in contrast, the egg contains all the material needed to initiate development. Therefore in addition to forming a haploid nucleus, oogenesis also builds up a store of cytoplasmic enzymes, mRNAs, organelles and metabolic substrates
Oocytes continuously die and only about 400 mature during a womans life time, explain more
between the 2 and 7 month of development about 7 million germ cells are formed. Most of the oogonia die before birth. The remaining oogonia become arrested in the first meiotic prophase. Only about 12 years later at puberty is meiosis completed
In oogenic meiosis how is the cytoplasm distributed?
it is unequally distributed between the daughter cells
oocyte maturation is arrested in the first meiotic prophase and actiavted by what?
progesterone
In some animal species meiosis is greatly modified. How so?
The oocyte remains diploid and therefore need not be fertilised to develop. this is called parthenogenesis
What are the primordial germ cells?
the precursors of the gametes - the sperm and egg
The PGCs form outside the ___ and migrate to the ___ during development
gonads
Until the 20th century it was believed that sex was determined by the __
environment
temperature and nutrition was thought to be important.
only after the rediscovery of Mendels work in 1900 and the discovery of the sex chromosome was a correlation made between sex chromosomes and sex determination
What is chromosomal sex determination?
In mammals the presence of either a second X chromosome or a Y chromosome determines if hte embryo is to be female or male
in birds the situation is reversed males are ZZ and females heterozygote ZW
What is sex determination like in insects?
the Y chromosome plays no role in sex determination, instead the ratio of sex chromosomes to autosomes determines the sex
In mammals what are the 2 types of sex determination?
primary and secondary.
Primary - determination of the gonads, this is determined by the sex chromosomes.
Secondary - determines the phenotype outside the gonads e.g. musculature, body size etc
Mammalian chromosomal sex determination results in what sort of sex ratio?
approximately equal
The mammalian gonads develop through a _____ stage. explain
bipotential or indifferent
genital ridge epithelium proliferates, germ cells migrate into gonads, the paired gonadal rudiments develop next to the kidneys
What is gonadal development like in males and females?
in males the sertoli cells in the testis cord secrete the anti mullerian hormone which blocks the development of the female ducts. Leydig cells produce testosterone, the Wolfifan duct is maintained.
In females each individual germ cell is surrounded by somatic cells. the mullerian duct is maintained. Due to the lack of testosterone the Wolffian duct degenerates. The mullerian duct develops into the oviduce, uterus etc
what is the Wolffian duct?
tube through which the sperm pass into the urethra
Why are clinical infertility studies useful in finding out which gene determines sex?
because the phenotype of mutations in sex determining genes is often sterility
Which gene determines sex in humans?
in humans the major gene for testis determination is located on the short arm of the Y chromosome.
This gene is called SRY and is a transcription factor.
what does SRY stand for?
sex determining region of the Y chromosome
Where is SRY expressed?
SRY is expressed in the somatic cells of the bipotential mouse gonads of XY mice immediately before these cells differentiate into sertoli cells.
What provides evidence that SRY controls male development?
XX mice which are transgenic for SRY develop into males in experiments
What other gene is also required for sex determination?
SOX9
what is SOX9
an autosomal gene that can induce testis formation.
what is evidence that SOX9 is implicated in sex determination?
XX humans who have an extra copy of SOX9 develop into males.
Knocking out the SOX( gene in the gonads of XY mice causes complete sexreversal.
SOX9 binds to the promotor of the gene for the ____hormone
anti mullerian
Which growth factor may be regulated by SRY or SOX9?
what evidence?
fibroblast growth factor 9
When Fgf9 is knocked out in mice, almost all mice become females.
Fgf9 causes proliferation of the sertoli precursors and stimulates their differentiation
Fgf9 is also required for bringing mesonepheric cells into the gonads
what is the role of the mesonepheric cells?
important in forming the testis cords
what evidence shows that the mesonepheric cells are important in forming the testis cords?
the gonad rudiment was removed from XX mice and combined with the XX or XY mesonephros of blue mice = no migration
the gonad rudiment was removed from XX mice and incubated in Fgf9 and then combined with mesonephric cells from blue mice = migration
Are there genes that produce the ovary?
at present there is no known gene that is ovary specific
which gene has been suggested to produce the ovary?
the gene DAX1 which is located on the X chromosome seems to antagonise the expression of the testis forming gene SRY.
2 copies of DAX1 supress SRY expression, male gonads do not develop.
what is secondary sex determination (more detail)
the development of the female and male phenotypes in response to hormones secreted by the ovaries and testis
what are the 2 phases of secondary sex determination?
within the embryo
at puberty
the formation of the male phenotype involves the secretion of 2 testicular hormones?
AMH - anti mullerian hormone
steroid hormone
where is the AMH made and what does it do?
sertoli cells
degeneration of the mullerian duct
where is the steroid hormone secreted? what do?
leydig cells
testosterone causes the Wolffian duct to differentiate into the internal and external male genitals
Why do people with androgen insensitivity syndrome develop as sterile women?
these XY individuals produce testosterone and AMH.
AMH causes the female mullerian duct to degenerate.
but they lack the receptor protein for testosterone and can therefore not respond to the testosterone made by the testis - no male reproductive organs
but they can respond to the estrogen made by adrenal glands - overall female appearance
despite their female appearance these women do not develop a uterus and oviducts because the mullerian duct degenerates
what is female pseudohermaphroditism?
the gonadal sex is female but the person is outwardly male
what causes female pseudohermaphroditism?
the most common cause is the overproduction of androgens (male hormones) in the ovary or in the adrenal gland due to the absence of an enzyme that metabolises cortisol steroids which results in accumulation of testosterone like steroids. the embryo is masculinised.
what are the sex differences in the brain that can be observed even before the gonads form?
XX embryonic rat brains have more epinephrin-expressing neurons than XY rat brains.
The SRY gene is not only expressed in the embryonic testis but also in the male embryonic and adult brain
In finches there are sex differences in the brain, what are they?
in male finches large regions of the brain are devoted to producing songs. female finches do not sing but if hormones are added experimentally singing can be induced in females.
how is sex determined in Drosophila melanogaster?
the y chromosome is not involved in determining sex. the y chromosome is important in sperm cell differentiation. the fruit flys sex is determined by a balance of female determinants on the x chromosomes to male determinants on the autosomes.
What are gynandromorhps?
half male and half female. there are no sex hormones in insects, each cell makes its own sexual decision. the loss of an x chromosome from one embryonic nucleus results in gynandromorphs in insects.
what is the sex determination cascade?
comes down to what type of mRNA is processed from the dsx transcript. If the ratio is 1 (2X:2A), Sxl is activated and causes the tra transcript to be spliced in female specific manner. Tra then interacts with tra2 to cause the dsx transcript to be spliced in a female specific manner. In males the double sex transcript is processed in a default manner to make the male specific message.
Male courtship behaviour is regulated by which protein in Drosophila?
Fruitless protein
What happens when fruitless is misexpressed in female flies?
they perform the entire male courtship ritual. try to mate with other female
Temperature dependent sex determination - alligator, red turtle, green turtle?
alligator = females at low temperature
red turtle = females at hot and cold temperatures
green turtle = females at hot temperature
How does temperature regulate sex determination? theory 1
cell proliferation and maleness
rapid cell divisions are required for testis formation (rapid production of sertoli cells). Higher temperatures could increase cell proliferation and direct gonadogenesis in the male direction
how does the temperature regulate sex determination? theory 2
hormones determine the sex
the enzyme aromatase which converts testosterone into estrogen may be critical in temperature dependent sex determination. If the aromatase level is low male offspring are produced. There is a correlation under natural conditions, male producing temperatures = low aromatase level
Pollutants introduced into the environment by humans can act like estrogens?
PCBs can reverse the sex of turtles raised at male temperatures. this knowledge is important for protecting endangered species.
