Your browser doesn't support javascript.
loading
Galectin-3 modulates postnatal subventricular zone gliogenesis.
Al-Dalahmah, Osama; Campos Soares, Luana; Nicholson, James; Draijer, Swip; Mundim, Mayara; Lu, Victor M; Sun, Bin; Tyler, Teadora; Adorján, István; O'Neill, Eric; Szele, Francis G.
Afiliación
  • Al-Dalahmah O; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Campos Soares L; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
  • Nicholson J; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Draijer S; Department of Oncology, University of Oxford, Oxford, UK.
  • Mundim M; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Lu VM; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Sun B; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Tyler T; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • Adorján I; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
  • O'Neill E; Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
  • Szele FG; Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Glia ; 68(2): 435-450, 2020 02.
Article en En | MEDLINE | ID: mdl-31626379
Postnatal subventricular zone (SVZ) neural stem cells generate forebrain glia, namely astrocytes and oligodendrocytes. The cues necessary for this process are unclear, despite this phase of brain development being pivotal in forebrain gliogenesis. Galectin-3 (Gal-3) is increased in multiple brain pathologies and thereby regulates astrocyte proliferation and inflammation in injury. To study the function of Gal-3 in inflammation and gliogenesis, we carried out functional studies in mouse. We overexpressed Gal-3 with electroporation and using immunohistochemistry surprisingly found no inflammation in the healthy postnatal SVZ. This allowed investigation of inflammation-independent effects of Gal-3 on gliogenesis. Loss of Gal-3 function via knockdown or conditional knockout reduced gliogenesis, whereas Gal-3 overexpression increased it. Gal-3 overexpression also increased the percentage of striatal astrocytes generated by the SVZ but decreased the percentage of oligodendrocytes. These novel findings were further elaborated with multiple analyses demonstrating that Gal-3 binds to the bone morphogenetic protein receptor one alpha (BMPR1α) and increases bone morphogenetic protein (BMP) signaling. Conditional knockout of BMPR1α abolished the effect of Gal-3 overexpression on gliogenesis. Gain-of-function of Gal-3 is relevant in pathological conditions involving the human forebrain, which is particularly vulnerable to hypoxia/ischemia during perinatal gliogenesis. Hypoxic/ischemic injury induces astrogliosis, inflammation and cell death. We show that Gal-3 immunoreactivity was increased in the perinatal human SVZ and striatum after hypoxia/ischemia. Our findings thus show a novel inflammation-independent function for Gal-3; it is necessary for gliogenesis and when increased in expression can induce astrogenesis via BMP signaling.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuroglía / Astrocitos / Ventrículos Laterales / Galectina 3 Límite: Animals Idioma: En Revista: Glia Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuroglía / Astrocitos / Ventrículos Laterales / Galectina 3 Límite: Animals Idioma: En Revista: Glia Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos