Sex Determination In Non Mammals Flashcards
What is DMRT1?
DMRT1
* Autosomal (chromosome 9). In humans, DMRT1 mutations can lead to sex reversal in XY individuals
* Overexpression o DMRT1 in embryonic gonads of genetically female (XX) mice leads to sex reversal
* DMRT1 encodes a TF related to the double sec gene of drosophila
* Expressed in differentiating testis but not ovary. Role in mammals seems to be to maintain but not initiate male specific gene expression and repress ovary-specific genes, e.g stimulates SOX9, represses WNT4 and FOXL2
Describe FoxL2 and CYP19a1
FoxL2 and cyp19a1
* cyp12a1 and foxL2 are both involved in female sex determination and are expressed in the developing ovary
* Cyp19a1 encodes aromatase, an enzyme that converts testosterone to oestrogen
* FoxL2 encodes a TF related that stimulates expression of cyp19a1 and so aromatase production
What are the way vertebrates sex can be determined?
Other classes of vertebrates
FoxL2 and cyp19a1
• cyp12a1 and foxL2 are both involved in female sex determination and are expressed in the developing ovary
• Cyp19a1 encodes aromatase, an enzyme that converts testosterone to oestrogen
• FoxL2 encodes a TF related that stimulates expression of cyp19a1 and so aromatase production
What sex steroids may influence gonad identity in non mammalian vertebrates?
Testosterone lead to development of testis
Oestrogens lead to development of ovaries
What does aromatase do?
Converts testosterone to oestrogen
What gene encodes aromatase
Cyp19a1
What is the ratio of oestrogen:testosterone dependent on?
The levels and activity of enzyme aromatase
What are the four main differences of birds to mammals?
- Females are heterogametic - ZW
- Gonad identity is influence by presence of oestrogen and testosterone- treatment of genetically female chicken embryos with aromatase inhibitors leads to testis differentiation and male development
- The DMRT1 gene is on the Z chromosome in bird-
4Sex determination in somatic cells is partly cell autonomous in chicken
How is sex determination different in xenopus?
Females are heterogametic
What happen if too much DMRT1 activity?
Low aromatase results in male
What happens if have low DMRT1 activity?
High aromatase
Leads to female
How can temp influence sex determination in fish?
Larvae raised at higher temps more likely to develop as males
Raised temps inhibit aromatase activity and reduce expression of the cyp19a1 gene
In xenopus what system is send an what gene is involved
Dm-w gene (present only on w chromosome) gives females by antagonising DMRT1 absence of dm-q give males
What is metamorphosis
A complex, irreversible post-embryonic developmental event that transforms the larval form of an animal into a radically different juvenile that only needs to grow and become sexually mature in order to become an adult.
What are the three types of changes that occur during metamorphosis of xenopus?
- Death and resorption of tadpole specific structures: resorption of tail (death of skin, notochord and muscle cells, ingestion of cell contents by macrophages)
- Growth of new frog-specific structures: formation of limbs, development of bone marrow
- Remodelling/reprogramming of existing cells and structures: shortening of gut and folding of gut epithelium, narrowing of head, movement of eyes to the top of the head, activation within liver cells of genes that encode urea cycle enzymes
Do metamorphic transitions happen simultaneously? why/why not?
no. transmforations need careful coordination so that new structures form before old structures are lost
What happens if young tadpoles are exposed to thyroid hormones
they metamorphose prematurely
what happens if thyroid glands in a tadpole fail to develop or are removed?
tadpoles fail to metamorphose and continue growing
What is cortisol needed for in metamorphosis?
to sensitise tissues to thyroid hormone
What is the main product of the thyroid gland
T4
What version of thyroid is inactive
reverse T3
What are the roles of the 2 types of deiodinase enzymes?
- Type II deiodinase D2 converts T4->T3 which is highly active
Type III deiodinase D3 converts T4->rT3 which is inactive
Why are the developing limbs more sensitive to circulating thyroid hormones than the tail?
- Limbs are able to make and respond to T3 throughout metamorphosis, hence limb development begins early
- Tail has little capacity to make T3 or respond to it during early metamorphosis so tail resorption occurs late
- Tail becomes able to make and respond to T3 late in metamorphosis because the rising levels of thyroid hormones induce expression in tail of TRs and D2
Which genes are regulated by thyroid hormones during metamorphosis (2 waves)?
- Thyroid hormone treatment of tadpole tissue induced 2 waves of gene activation or repression
- 1st wave = within a few hours of treatment, represent genes directly regulated by thyroid hormone. Some encode TFs or signalling proteins
- 2nd wave = appearing 24-48 hours after, represent gene s indirectly regulated by thyroid hormones, such as genes regulated by genes affected in the first wave
What does exposure of the tail to thyroid hormone cause
- Activates genes involved in cell death and tissue degradation
- Represses genes involved in biosynthesis and energy generation
What is neoteny
become sexually mature whilst in their larval state, and usually stay in that state throughout their life
What level of thyroid is needed for tail resorption
high levels
What level of thyroid is needed for lim formation
low levels
How do thyroid hormones result in signal transduction
- Thyroid hormones bind to thyroid receptors TRs located in the nucleus
- Act as ligand-responsive TFs
TRs bind to DNA sequences called thyroid response elements TREs that a re associated with TH-responsive genes. - TRs bind to TREs whether or not thyroid hormones are present. In absence of hormone, the receptor usually recruits a co-repressor proteins which repress the target genes, this prevents premature onset of metamorphosis
- When thyroid hormones bind to a TR, the receptor exchanges co-repressor proteins for co-activators, these activate the expression of the target gene
- Act as ligand-responsive TFs
What happens if the D2:D3 ratio is high or low?
- If D2:D3 ratio is high, most of the T4 that enters a cell is converted into T3
- If the D2:D3 ratio is low, most of the T4 that enters a cell is converted into inactive rT3
