BGDB Sexual Differentiation - Sex Determination: Difference between revisions
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| [[File:Macaque_Xi_at_interphase_02.jpg|300px]] | | [[File:Macaque_Xi_at_interphase_02.jpg|300px]] | ||
| '''1961''' - In order to have correct levels of X chromosome gene/protein expression (gene dosage), females must "inactivate" a single copy of the X chromosome (Xi) in each and every cell. | | valign="top" | '''1961''' - In order to have correct levels of X chromosome gene/protein expression (gene dosage), females must "inactivate" a single copy of the X chromosome (Xi) in each and every cell. | ||
Macaque Xi at interphase | Macaque Xi at interphase | ||
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| [[File:Model for XIST RNA spread from X inactivation center.jpg|300px]] | | [[File:Model for XIST RNA spread from X inactivation center.jpg|300px]] | ||
| '''1991''' - The initiator of the X inactivation process was discovered (1991) to be regulated by a region on the inactivating '''X chromosome encoding an X inactive specific transcript''' (XIST), that acts as RNA and does not encode a protein. Furthermore X inactivation occurs randomly throughout the embryo, generating a mosaic of maternal and paternally derived X chromosome activity in all tissues and organs. | | valign="top" | '''1991''' - The initiator of the X inactivation process was discovered (1991) to be regulated by a region on the inactivating '''X chromosome encoding an X inactive specific transcript''' (XIST), that acts as RNA and does not encode a protein. Furthermore X inactivation occurs randomly throughout the embryo, generating a mosaic of maternal and paternally derived X chromosome activity in all tissues and organs. | ||
Model for XIST RNA spread from X inactivation center | Model for XIST RNA spread from X inactivation center | ||
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| [[File:Stage7_primitive_streak_labelled.jpg|300px]] | | [[File:Stage7_primitive_streak_labelled.jpg|300px]] | ||
| Human Embryonic Disc (Stage 7) | | valign="top" | Human Embryonic Disc (Stage 7) | ||
* Primordial Germ Cells (PGCs) are thought to be the first population of cells to migrate through the primitive streak in early gastrulation. | * Primordial Germ Cells (PGCs) are thought to be the first population of cells to migrate through the primitive streak in early gastrulation. | ||
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* This population of cells then lie at the hindgut and yolk sac junctional region and later migrate into the germinal ridge in early embryonic development. | * This population of cells then lie at the hindgut and yolk sac junctional region and later migrate into the germinal ridge in early embryonic development. | ||
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| [[File:Mouse gonad sex determination 01.jpg|300px]] | | [[File:Mouse gonad sex determination 01.jpg|300px]] | ||
| Mouse gonad Sertoli and Germ Cells | | valign="top" | Mouse gonad Sertoli and Germ Cells | ||
* It is not the primordial germ cells which respond to SRY presence or absence, but the supporting cells within the developing gonad. | * It is not the primordial germ cells which respond to SRY presence or absence, but the supporting cells within the developing gonad. | ||
Revision as of 12:32, 29 May 2011
Practical 12: Sex Determination | Early Embryo | Late Embryo | Fetal | Postnatal | Abnormalities | 2011 Audio |
Introduction
Sex determination (male/female) at the biological level is determined by the presence or absence of the Y chromosome.
Initially, we did not know what this factor was and it was designated the "testis determining factor" (TDF). We now know (since 1990) that TDF is the protein product encoded by the SRY gene on the Y chromosome. Without this gene/protein the potential sex is female (see Male below).
For some time, female was considered the "default" sex in the absence of SRY, we now know this is not the case, with several genes specifically required for ovary formation. In females, sex determination involves at least one X chromosome gene, DAX1 encoding a nuclear hormone receptor.
Another critical genetic issue is related to the presence of two X chromosomes, "gene dosage", and in the case of mammals this is regulated by inactivating one of those X chromosomes in each and every cell (see Female below).
Male (XY)
Sry was discovered (1990) by studying a human XY female, resulting from a deletion in the Y chromosome that did not allow testis development. Subsequent mapping of this deletion allowed isolation and characterization of the SRY gene.
There is a suggestion that SRY may allow testes development by acting to inhibit DAX1, which is expressed in the indifferent gonad at the same time. The mechanism of an inhibitor inhibiting and inhibitor is seen in some other developing systems.
- encodes a 204 amino acid protein (Mr 23884 Da) that is a zinc-finger transcription factor.
- transcription factors bind to specific sites of DNA and regulates the transcription (expression) of other genes, we still do not know all the genes SRY regulates.
- expressed when testes begin to form, in gonadal tissue and does not require the presence of germ cells.
Notes: The Y chromosome is much smaller than the X chromosome and by definition, cannot contain important genes for other cellular functions.
Nomenclature, capital letters are used for human genes (SRY) and lower case letters are used for the equivalent genes in other species (sry).
Female (XX)
- In contrast to the Y chromosome, the X chromosome contains about 5% of the haploid genome and encodes house-keeping and specialized functions.
- The genetic content of the X chromosome has been strongly conserved between species.
- Links: Signaling in genital development | Fig. 1 - image | X Chromosome Inactivation - Epigenetics 1
Primordial Germ Cells
Practical 12: Sex Determination | Early Embryo | Late Embryo | Fetal | Postnatal | Abnormalities | 2011 Audio |
References
Additional Information
The information shown below is not part of today's Practical.
Genes implicated in sexual development in mammals
Table below modified from Table 1. Genes implicated in sexual development in mammals in recent review article.<pubmed>17237341</pubmed>| Physiol. Rev.
Gene | Protein Function | Gonad Phenotype of Null Mice | Human Syndrome | |
Bipotential gonad | ||||
Wt1 | Transcription factor | Blockage in genital ridge development | Denys-Drash, WAGR, Frasier syndrome | |
Sf1 | Nuclear receptor | Blockage in genital ridge development | Embryonic testicular regression syndrome | |
Lhx9 | Transcription factor | Blockage in genital ridge development | a | |
Emx2 | Transcription factor | Blockage in genital ridge development | a | |
M33 | Transcription factor | Gonadal dysgenesis | a | |
Testis-determining pathway | ||||
Gata4/Fog2 | Transcription/cofactor | Reduced Sry levels, XY sex reversal | a | |
Sry | Transcription factor | XY sex reversal | XY sex reversal (LOF); XX sex reversal (GOF) | |
Sox9 | Transcription factor | XY sex reversal | Campomelic dysplasia, XX sex reversal (GOF) | |
Sox8 | Transcription factor | XY sex reversal in combination with partial loss of Sox9 function | a | |
Fgf9 | Signaling molecule | XY sex reversal | a | |
Dax1 | Nuclear receptor | Impaired testis cord formation and spermatogenesis | Hypogonadism | |
Pod1 | Transcription factor | XY sex reversal | a | |
Dhh | Signaling molecule | Impaired differentiation of Leydig and PM cells | XY gonadal dysgenesis | |
Pgdra | Receptor | Reduction in mesonephric cell migration | a | |
Pgds | Enzyme | No phenotype | a | |
Arx | Transcription factor | Abnormal testicular differentiation | X-linked lissencephaly with abnormal genitalia | |
Atrx | Helicase | ND | ATRX syndrome | |
Insl3 | Signaling factor | Blockage of testicular descent | Cryptorchidism | |
Lgr8 | Receptor | Blockage of testicular descent | Cryptorchidism | |
Hoxa10 | Transcription factor | Blockage of testicular descent | Cryptorchidism | |
Hoxal1 | Transcription factor | Blockage of testicular descent | Cryptorchidism | |
Amh | Hormone | No Müllerian duct degeneration | Persistent Müllerian duct syndrome | |
Misrl1 | Receptor | No Müllerian duct degeneration | Persistent Müllerian duct syndrome | |
Pax2 | Transcription factor | Dysgenesis of mesonephric tubules | a | |
Lim1 | Transcription factor | Agenesis of Wolffian and Müllerian ducts | a | |
Dmrt1 | Transcription factor | Loss of Sertoli and germ cells | XY femaleb | |
Ovary-determining pathway | ||||
Wnt4 | Signaling molecule | Müllerian duct agenesis, testosterone synthesis, and coelomic vessel formation | XY female (GOF) | |
FoxL2 | Transcription factor | Premature ovarian failure | BPES | |
Dax1 | Nuclear receptor | XY sex reversal (GOF) | XY sex reversal (GOF) |
|
a No mutations in human sexual disorders identified to date. b Candidate gene for 9p deletion, XY sex reversal. |
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Cite this page: Hill, M.A. (2024, June 16) Embryology BGDB Sexual Differentiation - Sex Determination. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/BGDB_Sexual_Differentiation_-_Sex_Determination
- © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G