DMRT1
Doublesex- and mab-3-related transcription factor 1 (DM domain expressed in testis protein 1) [DMT1]
Publications[править]
Local signals maintain adult stem cells in many tissues. Whether the sexual identity of adult stem cells must also be maintained was not known. In the adult Drosophila testis niche, local Jak-STAT signaling promotes somatic cyst stem cell (CySC) renewal through several effectors, including the putative transcription factor Chronologically inappropriate morphogenesis (Chinmo). Here, we find that Chinmo also prevents feminization of CySCs. Chinmo promotes expression of the canonical male sex determination factor DoublesexM (Dsx(M)) within CySCs and their progeny, and ectopic expression of DsxM in the CySC lineage partially rescues the chinmo sex transformation phenotype, placing Chinmo upstream of Dsx(M). The Dsx homolog DMRT1 prevents the male-to-female conversion of differentiated somatic cells in the adult mammalian testis, but its regulation is not well understood. Our work indicates that sex maintenance occurs in adult somatic stem cells and that this highly conserved process is governed by effectors of niche signals. PAPERCLIP:
MeSH Terms
- Aging
- Animals
- Cell Differentiation
- Drosophila Proteins
- Drosophila melanogaster
- Gene Expression Regulation, Developmental
- Janus Kinases
- Male
- Nerve Tissue Proteins
- STAT Transcription Factors
- Sex Determination Processes
- Signal Transduction
- Stem Cell Niche
- Stem Cells
- Testis
- Transcription Factors
Sex in mammals is determined in the fetal gonad by the presence or absence of the Y chromosome gene Sry, which controls whether bipotential precursor cells differentiate into testicular Sertoli cells or ovarian granulosa cells. This pivotal decision in a single gonadal cell type ultimately controls sexual differentiation throughout the body. Sex determination can be viewed as a battle for primacy in the fetal gonad between a male regulatory gene network in which Sry activates Sox9 and a female network involving WNT/β-catenin signalling. In females the primary sex-determining decision is not final: loss of the FOXL2 transcription factor in adult granulosa cells can reprogram granulosa cells into Sertoli cells. Here we show that sexual fate is also surprisingly labile in the testis: loss of the DMRT1 transcription factor in mouse Sertoli cells, even in adults, activates Foxl2 and reprograms Sertoli cells into granulosa cells. In this environment, theca cells form, oestrogen is produced and germ cells appear feminized. Thus Dmrt1 is essential to maintain mammalian testis determination, and competing regulatory networks maintain gonadal sex long after the fetal choice between male and female. Dmrt1 and Foxl2 are conserved throughout vertebrates and Dmrt1-related sexual regulators are conserved throughout metazoans. Antagonism between Dmrt1 and Foxl2 for control of gonadal sex may therefore extend beyond mammals. Reprogramming due to loss of Dmrt1 also may help explain the aetiology of human syndromes linked to DMRT1, including disorders of sexual differentiation and testicular cancer.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Cell Transdifferentiation
- Female
- Feminization
- Forkhead Box Protein L2
- Forkhead Transcription Factors
- Gene Expression Regulation
- Granulosa Cells
- Male
- Mice
- Models, Biological
- Ovary
- RNA, Messenger
- SOX9 Transcription Factor
- Sertoli Cells
- Sex Characteristics
- Sex Determination Processes
- Sex Differentiation
- Testis
- Theca Cells
- Transcription Factors