University:
Amherst College
Course:
BIOL 220 | Developmental Biology
Academic year:

2021
Views:

229

Pages:

11
Author:

trepljajxxz

Secondary Sex Determination • Determination of non-gonadal differences – Females: oviduct, uterus, cervix, mammary glands – Males: vas deferens, seminal vesicle, penis, prostate glands – Also, non reproductive traits such as body size, vocal cords, musculature, etc. • Usually depends on primary sex determination Secondary Sex Determination • Experiment: • Remove gonad of young rabbit fetus before differentiation – XX Rabbit – XY Rabbit ----------> appears as female ----------> appears as female – Female = default path of secondary sex determination How is Primary Sex Determination Triggered? • Chromosomes: XX or XY? – What are the genes involved? – Compare to model systems (Drosophila, C.elegans) Testis Determining Factor • XX and XXX are female • XY and XXY are male – Must be a “testis determining factor on the Y chromosome” – Search for TDF • Sex-reversed Females: XY – deletion of short arm of Y • Sex-reversed Males: XX – addition of small piece from Y SRY • SRY identified – SRY = sex-determining region of the Y chromosome – Encodes a 223 a.a. protein – Transcriptional regulator of testes-specific genes • possible splicing factor – Where is SRY expressed? SRY Directs Male Development • Experiments with mice and SRY: – Mouse Sry is expressed in the bipotential gonad of males • Disappears after testes differentiate – Transgenic mice • inject Sry into pronuclei of newly fertilized mice • find some “male” looking mice that are actually XX – Other genes are necessary for testes determining ability: even genes on autosomes! Male Transgenic Male Development Also Requires Sox9 – Sox9 = autosomal gene required for testicular development – Expressed in genital ridges of males only, and in Sertoli cells throughout life – Conserved throughout vertebrates – Sex-reversed males: • XX lacking SRY – have extra copy of Sox9 • XX transgenic for Sox9 form testis – Transcriptional regulator • e.g. activates AMH gene (anti-Mullerian hormone) – Splicing regulator also Male Development Also Requires SF1 • SF1 (steroidogenic factor 1) – Transcription factor – Necessary for bipotential gonad – Expression drops in XX gonad but persists in XY gonad • Activates genes necessary for testosterone production (in Leydig cells) and AMH (in Sertoli cell) Dax1 on X Antagonizes SRY and Sox9 • Expressed in genital ridges (in both sexes) • Stays on in developing ovary • Turned off in developing testes • Gonadal dysgenesis female – XY but no deletion of Y – Instead an extra copy of Dax1 Dax1 acts as anti-testis gene in females Wnt4 May Be an OvaryDetermining Gene • Expressed in bipotential genital ridge • Expression lost in XY gonads, maintained in XX gonads • Activates Wnt4 • XX wnt4-/- mice fail to develop ovaries and instead gonads make AMH • XY humans with double wnt4 make extra DAX1 and ovary Partial Model of Vertebrate Sex Determination

Sex Determination Part 2

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