bicd130_06_lecture16r

bicd130_06_lecture16r - BICD 130 Embryos, Genes, and...

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Unformatted text preview: BICD 130 Embryos, Genes, and Development Paid Summer Intern Opportunity in Developmental Biology Position is with Linda Holland at SIO, studying amphioxus (a cephalochordate, a close relative of vertebrates) One month in the lab at SIO, remaining 6 weeks to 2 months in Florida Contact: lzholland@ucsd.edu 858-534-5607 Web: http://hollandlab.ucsd.edu/intro.htm Sexual Differentiation in Mammals Primary sex determination: Specification of the gonads; whether they differentiate as ovaries or testes Secondary sex determination: Specification of body phenotype for sexually dimorphic structures outside the gonads Primary Sex Determination in Mammals The Y chromosome carries a gene that encodes a testisdetermining factor Regulatory cascades controlling sexual phenotype in mammals FGF9 Gonadal tissue (genital ridge) derives from intermediate mesoderm The indifferent stage of human gonadal development Gonadal development in XX individual (external) Cord cells become granulosa cells; mesenchymal cells become thecal cells; together, these form the ovarian follicles Gonadal development in XY individual (internal or medullary) Cord cells become Sertoli cells; mesenchymal cells become Leydig cells Regulatory cascades controlling sexual phenotype in mammals C M C FGF9 M C = cord M = mesenchyme Mammalian genital ducts at the sexually indifferent stage Genital duct development in XY and XX individuals Regulatory cascades controlling sexual phenotype in mammals FGF9 Summary of gonad and duct development in mammals Regulatory cascades controlling sexual phenotype in mammals FGF9 Mammalian Sex Determination Genes SRY (HMG box TF) FGF9 (Soluble ligand) SOX9 (HMG box TF) SF1 (Nuclear receptor TF) DAX1 (Nuclear receptor TF) WNT4 (Soluble ligand) Sry gene in mammalian sex determination XY Transgenic XX Does SRY function as a splicing factor? RNA processing factor SC-35 and small nuclear RNA U6 are components of the spliceosome Mammalian genital ducts at the sexually indifferent stage Presence of Sry gene makes XY gonadal cells competent to induce mesonephric cell migration The mesonephric cells induce the XY gonadal epithelium to become Sertoli cells Treatment with FGF9 makes the XX gonad competent to induce mesonephric cell migration Sox9 confers a testis phenotype on the gonad of a transgenic XX mouse Regulatory cascades controlling sexual phenotype in mammals FGF9 DAX1 is a potential testis-suppressing gene Dax1 is expressed in the genital ridges of both XX and XY mice, but persists only in the XX gonadal rudiment Possible model for primary sex determination in mammals Sex Determination and Dosage Compensation in Drosophila Primary determinant: X/A ratio Three developmental outcomes affected: -germline sex -somatic sex -dosage compensation The X/A ratio is the primary determinant of sex in Drosophila Mechanisms of Dosage Compensation Mammals: X inactivation in XX Flies: X hypertranscription in XY Worms: X hypotranscription in XX Sex determination in the Drosophila female (XX) dpn Sex determination and dosage compensation in the Drosophila male (XY) dpn Activation of the Sex-lethal early promoter in the Drosophila female (XX) X No activation of the Sex-lethal early promoter in the Drosophila male (XY) Alternative splicing in the Drosophila sex determination cascade The female form of Doublesex acts both positively and negatively to promote female sexual development The male form of Doublesex acts both positively and negatively to promote male sexual development ...
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