title: Numb regulates somatic cell lineage commitment during early gonadogenesis in mice.
abstract: During early gonadogenesis, proliferating cells in the coelomic epithelium (CE) give rise to most of the somatic cells in both XX and XY gonads. Previous dye-labeling experiments showed that a single CE cell could give rise to additional CE cells and to both supporting and interstitial cell lineages, implying that cells in the CE domain are multipotent progenitors, and suggesting that an asymmetric division is involved in the acquisition of gonadal cell fates. We found that NUMB is asymmetrically localized in CE cells, suggesting that it might be involved. To test this hypothesis, we conditionally deletedNumbon aNumblmutant background just prior to gonadogenesis. Mutant gonads showed a loss of cell polarity in the surface epithelial layers, large interior cell patches expressing the undifferentiated cell marker LHX9, and a loss of differentiated cells in somatic cell lineages. These results indicate that NUMB is necessary for establishing polarity in CE cells, and that asymmetric divisions resulting from CE polarity are required for commitment to differentiated somatic cell fates. Surprisingly, germ cells, which do not arise from the CE, were also affected in mutants, which may be a direct or indirect effect of loss ofNumb.
authors.affiliation: Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Yi-Tzu
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Barske
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: DeFalco
authors.affiliation: Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA blanche.capel@duke.edu.
authors.forename: Blanche
authors.identifier: 0000-0002-6587-0969
authors.initials: B
authors.lastname: Capel
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division / Q000187:drug effects; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006066:Gonads / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004151:Dipeptides; D047908:Intracellular Signaling Peptides and Proteins; D060850:LIM-Homeodomain Proteins; C117058:Lhx9 protein, mouse; D008565:Membrane Proteins; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; C106292:Numbl protein, mouse; D051880:Receptors, Notch; D014157:Transcription Factors
keywords: Asymmetric cell division; Cell polarity; Coelomic epithelium; Mouse gonad; NOTCH; NUMB