title: Sdmg1 is a conserved transmembrane protein associated with germ cell sex determination and germline-soma interactions in mice.
abstract: In mammals, the supporting cell lineage in an embryonic gonad communicates the sex-determining decision to various sexually dimorphic cell types in the developing embryo, including the germ cells. However, the molecular nature of the sex-determining signals that pass from the supporting cells to the germ cells is not well understood. We have identified a conserved transmembrane protein, Sdmg1, owing to its male-specific expression in mouse embryonic gonads. Sdmg1 is expressed in the Sertoli cells of embryonic testes from 12.5 dpc, and in granulosa cells of growing follicles in adult ovaries. In Sertoli cells, Sdmg1 is localised to endosomes, and knock-down of Sdmg1 in Sertoli cell lines causes mis-localisation of the secretory SNARE Stx2 and defects in membrane trafficking. Upregulation of Sdmg1 appears to be part of a larger programme of changes to membrane trafficking pathways in embryonic Sertoli cells, and perturbing secretion in male embryonic gonads in organ culture causes male-to-female germ cell sex reversal. These data suggest that changes that occur in the cell biology of embryonic Sertoli cells may facilitate the communication of male sex-determining decisions to the germ cells during embryonic development.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Best
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Sahlender
authors.forename: Norbert
authors.initials: N
authors.lastname: Walther
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Peden
authors.forename: Ian R
authors.initials: IR
authors.lastname: Adams
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D012734:Disorders of Sex Development; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D012708:Sertoli Cells / Q000378:metabolism; D019849:Sex Determination Processes; D012733:Sex Differentiation; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D033921:Vesicular Transport Proteins
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; C522390:Tmem184a protein, mouse; D033921:Vesicular Transport Proteins