1. A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation
- Author
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Stephen Wincovitch, Shawn M. Burgess, Nisc Comparative Sequencing Program, Lisha Xu, Kade P Pettie, Claire Slevin, Zelin Chen, and Wuhong Pei
- Subjects
0301 basic medicine ,Biomedical Engineering ,Medicine (miscellaneous) ,lcsh:Medicine ,SMN1 ,Article ,03 medical and health sciences ,0302 clinical medicine ,SMN complex ,ErbB ,Genetics ,medicine ,Regeneration ,Gene ,Zebrafish ,030304 developmental biology ,0303 health sciences ,biology ,Regeneration (biology) ,lcsh:R ,Cell Biology ,Spinal muscular atrophy ,biology.organism_classification ,SMA ,medicine.disease ,Cell biology ,nervous system diseases ,030104 developmental biology ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Spinal muscular atrophy (SMA) is the most common genetic disease in children. SMA is generally caused by mutations in the gene SMN1. The survival of motor neurons (SMN) complex consists of SMN1, Gemins (2–8), and Strap/Unrip. We previously demonstrated smn1 and gemin5 inhibited tissue regeneration in zebrafish. Here we investigated each individual SMN complex member and identified gemin3 as another regeneration-essential gene. These three genes are likely pan-regenerative, since they affect the regeneration of hair cells, liver, and caudal fin. RNA-Seq analysis reveals that smn1, gemin3, and gemin5 are linked to a common set of genetic pathways, including the tp53 and ErbB pathways. Additional studies indicated all three genes facilitate regeneration by inhibiting the ErbB pathway, thereby allowing cell proliferation in the injured neuromasts. This study provides a new understanding of the SMN complex and a potential etiology for SMA and potentially other rare unidentified genetic diseases with similar symptoms.
- Published
- 2020