MASH1/Ascl1a leads to GAP43 expression and axon regeneration in the adult CNS

PloS One
Ryan R WilliamsMary Bartlett Bunge

Abstract

Unlike CNS neurons in adult mammals, neurons in fish and embryonic mammals can regenerate their axons after injury. These divergent regenerative responses are in part mediated by the growth-associated expression of select transcription factors. The basic helix-loop-helix (bHLH) transcription factor, MASH1/Ascl1a, is transiently expressed during the development of many neuronal subtypes and regulates the expression of genes that mediate cell fate determination and differentiation. In the adult zebrafish (Danio rerio), Ascl1a is also transiently expressed in retinal ganglion cells (RGCs) that regenerate axons after optic nerve crush. Utilizing transgenic zebrafish with a 3.6 kb GAP43 promoter that drives expression of an enhanced green fluorescent protein (EGFP), we observed that knock-down of Ascl1a expression reduces both regenerative gap43 gene expression and axonal growth after injury compared to controls. In mammals, the development of noradrenergic brainstem neurons requires MASH1 expression. In contrast to zebrafish RGCs, however, MASH1 is not expressed in the mammalian brainstem after spinal cord injury (SCI). Therefore, we utilized adeno-associated viral (AAV) vectors to overexpress MASH1 in four month old rat (Rattus no...Continue Reading

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Citations

Feb 9, 2016·Experimental Neurology·Stephanie M FogersonJennifer R Morgan
Mar 5, 2016·Experimental Neurology·Jeffrey P Rasmussen, Alvaro Sagasti
Apr 3, 2016·Environmental Pollution·Qin WuGuangyu Li
Dec 28, 2016·Neuroscience Letters·Ishwariya Venkatesh, Murray G Blackmore
Jul 29, 2018·Molecular Neurobiology·Chao LiZheng Gang Zhang
Aug 22, 2017·Frontiers in Cellular Neuroscience·Vinicius T Ribas, Marcos R Costa

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Methods Mentioned

BETA
transgenic
fluorescence microscopy
PCR
immunoprecipitation

Clinical Trials Mentioned

NCT01739023

Software Mentioned

Graph Pad Prism

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