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Radial glia promote microglial development through integrin αVß8 -TGFß1 signaling.
McKinsey, Gabriel L; Santander, Nicolas; Zhang, Xiaoming; Kleemann, Kilian; Tran, Lauren; Katewa, Aditya; Conant, Kaylynn; Barraza, Matthew; Waddell, Kian; Lizama, Carlos; La Russa, Marie; Koo, Hyun Ji; Lee, Hyunji; Mukherjee, Dibyanti; Paidassi, Helena; Anton, E S; Atabai, Kamran; Sheppard, Dean; Butovsky, Oleg; Arnold, Thomas D.
Afiliación
  • McKinsey GL; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
  • Santander N; Instituto de Ciencias de la Salud, Universidad de ÓHiggins, Rancagua, Chile.
  • Zhang X; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Kleemann K; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Tran L; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
  • Katewa A; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
  • Conant K; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
  • Barraza M; Northwestern University, Department of Neuroscience, Chicago, IL, USA.
  • Waddell K; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
  • Lizama C; University of California San Francisco, Cardiovascular Research Institute, San Francisco, CA, USA.
  • La Russa M; Stanford University, Department of Bioengineering, Stanford, CA, USA.
  • Koo HJ; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
  • Lee H; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
  • Mukherjee D; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
  • Paidassi H; CIRI Centre International de Recherche en Infectiologie, Univ Lyon Inserm U1111 Université Claude Bernard Lyon 1 CNRS UMR5308 ENS de Lyon F-69007 Lyon France.
  • Anton ES; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Atabai K; University of California San Francisco, Cardiovascular Research Institute, San Francisco, CA, USA.
  • Sheppard D; University of California San Francisco, Cardiovascular Research Institute, San Francisco, CA, USA.
  • Butovsky O; Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Arnold TD; University of California San Francisco, Department of Pediatrics and Newborn Brain Research Institute, San Francisco, CA, USA.
bioRxiv ; 2023 Sep 21.
Article en En | MEDLINE | ID: mdl-37790363
ABSTRACT
Microglia diversity emerges from interactions between intrinsic genetic programs and environment-derived signals, but how these processes unfold and interact in the developing brain remains unclear. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) expressed in radial glia progenitors activates microglia-expressed TGFß1, permitting microglial development. Domain-restricted deletion of Itgb8 in these progenitors establishes complementary regions with developmentally arrested "dysmature" microglia that persist into adulthood. In the absence of autocrine TGFß1 signaling, we find that microglia adopt a similar dysmature phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the TGFß signal transducers Smad2 and Smad3 have a less polarized dysmature phenotype and correspondingly less severe neuromotor dysfunction. Finally, we show that non-canonical (Smad-independent) signaling partially suppresses disease and development associated gene expression, providing compelling evidence for the adoption of microglial developmental signaling pathways in the context of injury or disease.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos