Abstract
RAFAEL JIMI~NEZ*, ANTONIO S,6NCHEZ :t:, MIGUEL BURGOS AND RAFAEL DiAZ DE LA GUARDIA mburgos@goliat.ugr.es DEPART&~IEYFO DE GENETIC.A, FACb'LTAD DE CIE.XClM, UNIVERSIDAD DE GP,&'~ADA, r UENqF2~a:'EVA S/N, E-18071 GR~'~ADA, SPAIN. * DEPARTa.',IEVfO DE BIOLOGiA EXPEPL~IEN'rAL Y CIENCIAS DE LA SALUD, FA~'LTAD DE CIENC1AS F.2(PERL'*~N'rALES, UNIVERSIDAD DE JAEN, Mammals possess an XX/XY chromo- somal system for sex determination. The presence of SRY, a master- regulatory gene on the Y chromosome, is necessary to induce the undifferen- tiated, bipotential gonadal primor- dium (the embryonic genital ridge) to develop as a testis. In the absence of SRY, it develops as an ovary I. Once the gonads differentiate, their male- or female-specific endocrine function is responsible for the rest of the events involved in the pheno~pic ~_~..'.=l dif- fcrenuation process 2. Accordingly, in mammals, sex determination can be equated with testis determination. SRY is the only gene currently known to be involved in the process of sex determination. A number of cloned genes probably participate in gonadal development: the Mtillerian inhibiting substance gene (MIS; also called the antimiillerian hormone gene, AMH)3, the SRY-related gene, SOX9 (ReL 4), the mouse gene en- coding steroidogenic factor (SF1), FtzF1 (Ref. 5), the X-linked gene, DAXI (Refs 6, 7), and the Wilm's tumor suppressor gene, WT1 (Ref. 8). Whereas MIS and SOX9 are probably involved in the male pathway, the moment and site of action of the rest of these genes in the sex-differ- entiation process is unclear. FtzF1 and WT1 might be involved in the formation of the bipotential gonad, thus acting before SRY. The female pathway remains almost completely unknown. An X-linked, dosage-sen- sitive gene (DSS), which might be identical to DAXI, causes male-to- female sex reversal when duplicated, anti has been proposed to be a member of the female pathway 9.1°, but the findings on this point are inconclusive (see below). Therefore, mammalian sex-determination is, in fact, an unsolved genetic puzzle from which a number of pieces are prob- at~ly still missing.
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