Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion.
Glial cells have been classically described as supporting cells for neurons. Recently, additional roles during neural development have begun to emerge. Here, we report that ventral midbrain glia, including astrocytes and radial glia, are the source of signals required by neural precursors to acquire a dopaminergic phenotype. We found that ventral midbrain glia, but not cortical glia, secrete high levels of the glycolipoprotein Wnt-5a, express region-specific transcription factors such as Pax-2, En-1 and Otx-2 and increase the differentiation of cortical or ventral midbrain Nurr1 precursors into tyrosine hydroxylase-positive neurons. Moreover, blocking experiments using a Wnt-5a blocking antibody indicated that the effects of ventral midbrain glia on Nurr1-positive neural precursors are partially mediated by Wnt-5a. Thus, our results identify Wnt-5a as an important component of the dopaminergic inductive activity of the ventral midbrain glia.
Castelo-Branco
Gonçalo
G
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheeles vag 1, A1, plan 2, 17177 Stockholm, Sweden.
Sousa
Kyle M
KM
Bryja
Vitezslav
V
Pinto
Luisa
L
Wagner
Joseph
J
Arenas
Ernest
E
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D008636:Mesencephalon / Q000033:anatomy & histology / Q000166:cytology* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
D000906:Antibodies; D004268:DNA-Binding Proteins; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; D004298:Dopamine