Bone morphogenetic protein signaling regulates Id1-mediated neural stem cell quiescence in the adult zebrafish brain via a phylogenetically conserved enhancer module. (11th April 2020)

• Record Type: Journal Article
• Authors: Zhang, Gaoqun; Ferg, Marco; Lübke, Luisa; Takamiya, Masanari; Beil, Tanja; Gourain, Victor; Diotel, Nicolas; Strähle, Uwe; Rastegar, Sepand
• Is Part Of: Stem cells. Volume 38:Number 7(2020)
• Page Start: 875
• Page End: 889
• Publication Date: 2020-04-11
• Subjects: adult neurogenesis -- BMP -- cis-regulatory modules -- id1 -- neural stem cell -- radial glial cell -- regeneration -- telencephalon -- transcription -- zebrafish; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.3182
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: In the telencephalon of adult zebrafish, the inhibitor of DNA binding 1 ( id1 ) gene is expressed in radial glial cells (RGCs), behaving as neural stem cells (NSCs), during constitutive and regenerative neurogenesis. Id1 controls the balance between resting and proliferating states of RGCs by promoting quiescence. Here, we identified a phylogenetically conserved cis-regulatory module (CRM) mediating the specific expression of id1 in RGCs . Systematic deletion mapping and mutation of conserved transcription factor binding sites in stable transgenic zebrafish lines reveal that this CRM operates via conserved smad1/5 and 4 binding motifs under both homeostatic and regenerative conditions. Transcriptome analysis of injured and uninjured telencephala as well as pharmacological inhibition experiments identify a crucial role of bone morphogenetic protein (BMP) signaling for the function of the CRM. Our data highlight that BMP signals control id1 expression and thus NSC proliferation during constitutive and induced neurogenesis. : Abstract : The bone morphogenetic protein (BMP) pathway controls inhibitor of DNA binding 1 ( id1 ) expression in the radial glial cells (RGCs) during both constitutive and regenerative neurogenesis. An evolutionary conserved cis-regulatory module (CRM) of id1 is necessary for its RGC-specific expression. The id1 CRM contains a BMP responsive element, which is necessary but not sufficient for the expression of id1 in the ventricular zone of the zebrafish adult telencephalon. The human CRM2 works in zebrafish. Thus its function was conserved during evolution.