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AGS3 antagonizes LGN to balance oriented cell divisions and cell fate choices in mammalian epidermis.
Descovich, Carlos P; Lough, Kendall J; Jena, Akankshya; Wu, Jessica J; Yom, Jina; Spitzer, Danielle C; Uppalapati, Manuela; Kedziora, Katarzyna M; Williams, Scott E.
Afiliación
  • Descovich CP; Department of Pathology and Laboratory Medicine and Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
  • Lough KJ; Curriculum in Cell Biology & Physiology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, United States.
  • Jena A; Department of Pathology and Laboratory Medicine and Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
  • Wu JJ; Department of Pathology and Laboratory Medicine and Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
  • Yom J; Department of Pathology and Laboratory Medicine and Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
  • Spitzer DC; Department of Pathology and Laboratory Medicine and Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
  • Uppalapati M; Department of Pathology and Laboratory Medicine and Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
  • Kedziora KM; Department of Pathology and Laboratory Medicine and Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States.
  • Williams SE; Bioinformatics and Analytics Research Collaborative, University of North Carolina at Chapel Hill, Chapel Hill, United States.
Elife ; 122023 04 05.
Article en En | MEDLINE | ID: mdl-37017303
Oriented cell divisions balance self-renewal and differentiation in stratified epithelia such as the skin epidermis. During peak epidermal stratification, the distribution of division angles among basal keratinocyte progenitors is bimodal, with planar and perpendicular divisions driving symmetric and asymmetric daughter cell fates, respectively. An apically restricted, evolutionarily conserved spindle orientation complex that includes the scaffolding protein LGN/Pins/Gpsm2 plays a central role in promoting perpendicular divisions and stratification, but why only a subset of cell polarize LGN is not known. Here, we demonstrate that the LGN paralog, AGS3/Gpsm1, is a novel negative regulator of LGN and inhibits perpendicular divisions. Static and ex vivo live imaging reveal that AGS3 overexpression displaces LGN from the apical cortex and increases planar orientations, while AGS3 loss prolongs cortical LGN localization and leads to a perpendicular orientation bias. Genetic epistasis experiments in double mutants confirm that AGS3 operates through LGN. Finally, clonal lineage tracing shows that LGN and AGS3 promote asymmetric and symmetric fates, respectively, while also influencing differentiation through delamination. Collectively, these studies shed new light on how spindle orientation influences epidermal stratification.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Portadoras / Proteínas de Ciclo Celular Límite: Animals Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Portadoras / Proteínas de Ciclo Celular Límite: Animals Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido