Endocrine glands in the human brain Development of anterior pituitary gland 1. The oral end of the gut is blocked by a region of ectoderm called the oral plate or stomodeum. 2. The stomodeum breaks and forms the oral opening of the digestive tube. 3. The stomodeum is in contact with the brain ectoderm, and interact each other. 4. The roof of stomodeum forms Rathke’s pouch and becomes the glandular portion of the pituitary gland.Formation of the human digestive system 28 days embryo Anterior pituitary or adenohypophysis: Glandular portion of the pituitary gland. Rathke’s pouch Development of posterior pituitary gland 1. The neural tissue on the floor of the diencephalon forms the in fundibulm 2. The neural infundibulum becomes to the neural portion of the pituitary.Formation of the human digestive system 28 days embryo Posterior pituitary or neurohypophysis: Neural portion of the pituitary. Infundibulum Development of posterior pituitary gland 1. Rathke's pouch grows upwards from the roof of stomodeum. 2. The infundibulum grows downwards from the floor of diencephalon. 3. Rathke's pouch pinchs off from the stomodeum. 4. Rathke's pouch proliferate to form the pars distalis. 5. Rathke's pouch extends up the anterior aspect of the infundibulum as the pars tuberallis. 6. The posterior surface of Rathke's pouch does not proliferate but forms the poorly developed pars intermedia. http://www.med.mun.ca/anatomyts/head/pit.htm Adenohypophysis (Anterior pituitary) Neurohypophysis (Posterior pituitary) Feedback loop in endocrine system CHAPTER 17, OPENERPrimary sex determination in mammals The Y chromosome carries a gene that encodes a testis-determining factor. XXXXXY would be male; XO would be female. Vertebrate sex determination systems Ezaz et al., Current Biology 2006 “Multiple”: involvement of more than one pair of chromosomes in sex determination. TSD: temperature-dependent sex determination. Postulated cascades of sex determination in mammals Other than this cue, vertebrates are using the similar genes & cascades in sex determination. Primary sex determination Secondary sex determination Differentiation of human gonads shown in transverse section Bipotential gonad The gonadal rudiments are paired regions of the intermediate mesoderm; they form adjacent to the developing kidneys. Testis development in human  Somatic cells  Sertoli cells  Testis cords  Seminiferous tubules  Testis cords (medulla)  Rete testis  Interstitial mesenchyme cells  Leydig cells  Tubules of mesonephros  Efferent ductSeminiferous tubule in mammal  Germ cells  Forming sperm  Sertoli cells  nurture the developing sperm cells  Leydig cells  Synthesize and secrete androgens Differentiation of human gonads shown in transverse section  Somatic cells  granulosa cells  Mesenchyme cells  Theca cells  The germ cell, theca cells and granulosa cells  Follicles The germ cells accumulate near the outer surface of the gonad. Mature ovarian follicle  Germ cell  Forming egg  Theca cells  Producing androstenedione  Granulosa cells  Producing estradiol The development of the gonads and their ducts in mammals Bipotential gonad The development of the gonads and their ducts in mammals Regress Müllerian duct Regress Wolffian duct Summary of the results after the sex determination & differentiation• SRY: The Y chromosome sex determination • SOX9: An autosomal testis-determining gene • Fibroblast growth factor 9 • SF1: The link between SRY and the male developmental pathway • DAX1: A potential testis-suppressing gene on the X chromosome • WNT4: A potential ovary-determining gene on an autosome Mechanisms of primary sex determination Postulated cascades of sex determination in mammalsAn XX mouse transgenic for Sry is male • SRY, sex determining region of the Y chromosome specific in mammals. • A transcription factor with the HMG (high-mobility group) box. PCR XY♂ XX♂ XX+Sry Ability of Sox9 to generate testes  SOX9, SRY-box 9 (campomelic dysplasia, autosomal sex-reversal)  A HMG-box protein on an autosome  XX + SOX9 ➡ ♂ in human & mouse  XY – SOX9 ➡ ♀ in mouse in Sertoli cells SRY & SOX9 on sex determination  SRY might act as a “switch” to activate SOX9, and SOX9 may initiate the conserved evolutionary pathway to testis formation. 1. What activates SRY gene? 2. What does SRY protein activate? 3. How might this activation work? 4. Is SOX9 gene activated by SRY? 5. What genes does SOX9 activate? Migration of the mesonephric cells into Sry+ gonadal rudiments  Without SRY ➡ No migration of mesonephric cells into gonad. Migration of the mesonephric cells into Sry+ gonadal rudiments  With FGF9 ➡ Migration of mesonephric cells into gonad can be induced. Intimate relation between the mesonephric ducts and developing gonad  Mesonephric cells are important in forming the testis cords, directly and indirectly. 1. Contribute directly to the cords. 2. Help organize the Sertoli cell precursors to form the cords. SF1: The link between SRY and the male developmental pathway  Steroidogenic factor 1 (SF1): NR5A1;adrenal4bindingprotein(Ad4BP);fushitarazufactorhomolog1(Ftzf1);nuclearreceptorAdBP4;steroidhormonereceptorAd4BP;.  Necessarytomakethebipotentialgonad.  Levelsdeclineinfemalegonad.  It stays on in male gonad, and works with SOX1  AMH transcription in Sertoli cells.  Steroidogenesis in Leydig cells.Phenotypic sex reversal in humans having two copies of the DAX1 locus In XY embryos, DAX1 would be suppressed, but having two active copies of the gene would override this suppression. Dax1 expression in the mouse genital ridge Both XY & XX in the bipotential gonad Only in XX gonad Dax1 antagonize the function of Sry & Sox9, and down-regulates Sf1 expression. Possible mechanism for primary sex determination in mammalsThemolecularandgeneticeventsinmammaliansexdetermination. SekidoandLovell-Badge,TrendsinGenetics(2009) The right time and the right place  Timing is critical.  There may be a brief window of time wherein the testis-forming genes can function. If