BGDB Sexual Differentiation - Sex Determination: Difference between revisions
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==Introduction== | ==Introduction== | ||
[[File: | [[File:Male XY karyotype.jpg|thumb|200px|X and Y chromosomes]] | ||
Sex determination (male/female) at the biological level is determined by the presence or absence of the | Sex determination (male/female) at the biological level is determined by the presence or absence of the {{ChrY}} 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 | 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 {{ChrY}} 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 | 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 {{ChrX}} 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). | 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)== | ==Male (XY)== | ||
[[File:Human_Y_chromosome_SRY_region.jpg|thumb|200px|alt=Human Y chromosome showing SRY region|link=Y Chromosome|Human Y chromosome showing SRY region]] | |||
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. | 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. | ||
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Nomenclature, capital letters are used for human genes (SRY) and lower case letters are used for the equivalent genes in other species (sry). | Nomenclature, capital letters are used for human genes (SRY) and lower case letters are used for the equivalent genes in other species (sry). | ||
{| | |||
|- | |||
| colspan=5|[[Developmental Signals - Sox|Table - Human Sox Family]] | |||
|-bgcolor="CEDFF2" | |||
! width=100px|Approved<br>Symbol | |||
! width=100px|Approved Name | |||
! Previous Symbols | |||
! Synonyms | |||
! Chromosome | |||
|-bgcolor="F5FAFF" | |||
| [https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=11311 SRY] || sex determining region Y || || TDF || {{ChrY}}p11.2 | |||
|- | |||
|} | |||
:'''Links:''' [http://physrev.physiology.org/content/87/1/1/F6.expansion.html Sex reversal in humans caused by abnormal X-Y exchange] | [http://physrev.physiology.org/content/87/1/1/F6.large.jpg Fig. 2 - image] | :'''Links:''' [http://physrev.physiology.org/content/87/1/1/F6.expansion.html Sex reversal in humans caused by abnormal X-Y exchange] | [http://physrev.physiology.org/content/87/1/1/F6.large.jpg Fig. 2 - image] | ||
==Female (XX)== | ==Female (XX)== | ||
[[File:Human X chromosome.jpg|thumb|200px|link=X Chromosome|Human X chromosome showing some known genetic disorders.]] | |||
* In contrast to the Y chromosome, the {{ChrX}} chromosome contains about 5% of the haploid genome and encodes house-keeping and specialized functions. | |||
* In contrast to the Y chromosome, the | |||
* The genetic content of the X chromosome has been strongly conserved between species. | * The genetic content of the X chromosome has been strongly conserved between species. | ||
{| | {| | ||
| [[File:Macaque_Xi_at_interphase_02.jpg| | | [[File:Macaque_Xi_at_interphase_02.jpg|300px]] | ||
Macaque Xi at interphase | Macaque Xi at interphase | ||
| '''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. | |||
* this inactivated chromosome can be identified in female blood cells as the "Barr body". | |||
[[File:Neutrophil EM01.jpg|alt=Neutrophil Barr body|link=Molecular Development - X Inactivation|300px]] | |||
A female human neutrophil - Barr body (White arrowhead){{#pmid:22945932|PMID22945932}} | |||
|- | |- | ||
| [[File:Model for XIST RNA spread from X inactivation center.jpg| | | [[File:Model for XIST RNA spread from X inactivation center.jpg|300px]] | ||
Model for XIST RNA spread from X inactivation center | Model for XIST RNA spread from X inactivation center | ||
| '''1991''' - The initiator of the X inactivation process was discovered. | |||
* regulated by a region on the inactivating '''X chromosome encoding an X inactive specific transcript''' (XIST). | |||
* 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. | |||
|} | |} | ||
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{| | {| | ||
| [[File:Stage7_primitive_streak_labelled.jpg|300px]] | | [[File:Stage7_primitive_streak_labelled.jpg|300px]] | ||
'''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. | ||
Week 3 | |||
* Human embryonic disc showing the primitive streak region where gastrulation occurs, generation the trilaminar embryo. | |||
* Arrows indicate direction of cell migration through the streak. | |||
|- | |- | ||
| | | [[File:Stage9 bf2-primordial germ cell region.jpg|300px]] | ||
'''Human Embryo''' (Stage 9) primordial germ cell region | |||
| | | | ||
* 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. | ||
|- | |- | ||
| [[File:Mouse gonad sex determination 01.jpg|300px]] | | [[File:Mouse gonad sex determination 01.jpg|300px]] | ||
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. | ||
'''Sry Signaling'''{{#pmid:16700629|PMID16700629}} | |||
* '''red''' - Sertoli cells, showing Fgf9 expression (following Sry expression FGF9 is a downstream signaling molecule). | |||
* '''green''' - Germ cells and endothelial cells, showing PECAM expression. | |||
|} | |||
<br> | |||
{{BGDB Sexual Differentiation - Sex Determination Interactive}} | |||
<br> | |||
{{BGDB SexDiffn}} | |||
==Additional Information== | |||
{{Med Prac additional Information}} | |||
[[File:Mouse- gonadal supporting cell development.jpg|600px]] | |||
Mouse - gonadal supporting cell development | |||
===Sexual Development Genes=== | |||
{{Sex development genes table}} | |||
{| | |||
! X Inactivation | |||
|- | |||
| width=155px|[[File:Mary Lyon.jpg|150px|link=Embryology History - Mary Lyon]] | |||
Mary Lyon | |||
| For information about the discovery of X inactivation see also the [[Embryology History - Mary Lyon|interview with Mary Lyon]]. | |||
PSH - One of the things which I have been asking everybody I see has been, which particular piece of work or part of their work over the years, if you just had to choose one, which would you feel you identify most closely with, or feel most affection for. I know it’s difficult to ask, but could you single out an area, or is it really not possible. | |||
ML - I think the X inactivation. | |||
(More? {{X Inactivation}}) | |||
|} | |} | ||
===Dmrt1 and Foxl2=== | |||
{{#pmid:28091399}} | |||
:"However, recent studies in mice have provided evidence that it is possible for the gonadal sex phenotype to be switched even in adulthood. These studies have shown that two key genes, doublesex and mad-3 related transcription factor 1 ([https://www.omim.org/entry/602424 Dmrt1]) and forkhead box L2 ([https://www.omim.org/entry/605597 Foxl2]), function in a Yin and Yang relationship to maintain the fates of testes or ovaries in adult mammals, and that mutations in either gene might have a dramatic effect on gonadal phenotype. Thus, adult gonad maintenance in addition to fetal sex determination may both be important for the fertility." | |||
{{ | |||
{{Genital terms}} | |||
==References== | ==References== | ||
<references/> | <references/> | ||
{{BGDBFooter}} | |||
{{ | [[Category:Sry]] |
Latest revision as of 12:55, 3 June 2019
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).
Table - Human Sox Family | ||||
Approved Symbol |
Approved Name | Previous Symbols | Synonyms | Chromosome |
---|---|---|---|---|
SRY | sex determining region Y | TDF | Yp11.2 |
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.
Macaque Xi at interphase |
1961 - In order to have correct levels of X chromosome gene/protein expression (gene dosage).
A female human neutrophil - Barr body (White arrowhead)[1] |
Model for XIST RNA spread from X inactivation center |
1991 - The initiator of the X inactivation process was discovered.
|
- Links: Signaling in genital development | Fig. 1 - image | X Chromosome Inactivation - Epigenetics 1
Primordial Germ Cells
Human Embryonic Disc (Stage 7) |
|
Human Embryo (Stage 9) primordial germ cell region |
|
Mouse gonad Sertoli and Germ Cells |
|
Sex Determination Interactive Component
Attempt the Quiz - Sex Determination | ||
---|---|---|
Here are a few simple Quiz questions that relate to Sex Determination from the lecture and practical.
|
Practical 12: Sex Determination | Early Embryo | Late Embryo | Fetal | Postnatal | Abnormalities | 2011 Audio |
Additional Information
Additional Information - Content shown under this heading is not part of the material covered in this class. It is provided for those students who would like to know about some concepts or current research in topics related to the current class page. |
Mouse - gonadal supporting cell development
Sexual Development Genes
Gene (OMIM) | 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 | |
Hoxa11 | 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) | |
RSPO1 | Signaling molecule | XX sex reversal (LOF) | XX sex reversal (LOF) | |
Table Legend | ||||
|
a No mutations in human sexual disorders identified to date.
b Candidate gene for 9p deletion, XY sex reversal. | |||
Table data modified[3] |
X Inactivation | |
---|---|
Mary Lyon |
For information about the discovery of X inactivation see also the interview with Mary Lyon.
PSH - One of the things which I have been asking everybody I see has been, which particular piece of work or part of their work over the years, if you just had to choose one, which would you feel you identify most closely with, or feel most affection for. I know it’s difficult to ask, but could you single out an area, or is it really not possible. ML - I think the X inactivation. (More? X Inactivation) |
Dmrt1 and Foxl2
Huang S, Ye L & Chen H. (2017). Sex determination and maintenance: the role of DMRT1 and FOXL2. Asian J. Androl. , 19, 619-624. PMID: 28091399 DOI.
- "However, recent studies in mice have provided evidence that it is possible for the gonadal sex phenotype to be switched even in adulthood. These studies have shown that two key genes, doublesex and mad-3 related transcription factor 1 (Dmrt1) and forkhead box L2 (Foxl2), function in a Yin and Yang relationship to maintain the fates of testes or ovaries in adult mammals, and that mutations in either gene might have a dramatic effect on gonadal phenotype. Thus, adult gonad maintenance in addition to fetal sex determination may both be important for the fertility."
Genital System Terms (expand to view) |
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Note there are additional glossaries associated with spermatozoa, oocyte renal.
|
Other Terms Lists |
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References
- ↑ Brinkmann V & Zychlinsky A. (2012). Neutrophil extracellular traps: is immunity the second function of chromatin?. J. Cell Biol. , 198, 773-83. PMID: 22945932 DOI.
- ↑ Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, Poulat F, Behringer RR, Lovell-Badge R & Capel B. (2006). Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol. , 4, e187. PMID: 16700629 DOI.
- ↑ Wilhelm D, Palmer S & Koopman P. (2007). Sex determination and gonadal development in mammals. Physiol. Rev. , 87, 1-28. PMID: 17237341 DOI.
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Cite this page: Hill, M.A. (2024, May 2) 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