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.

Details

Title
A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation
Author
Pei Wuhong 1 ; Xu, Lisha 1 ; Chen Zelin 1 ; Slevin, Claire C 1 ; Pettie, Kade P 1   VIAFID ORCID Logo  ; Wincovitch, Stephen 2 ; Barnabas, Beatrice B 3 ; Black, Sean 3 ; Bouffard, Gerard G 3 ; Brooks, Shelise Y 3 ; Coleman, Holly 3 ; Dekhtyar Lyudmila 3 ; Guan Xiaobin 3 ; Han, Joel 3 ; Shi-ling, Ho 3 ; Legaspi Richelle 3 ; Maduro, Quino L 3 ; Masiello, Catherine A 3 ; McDowell, Jennifer C 3 ; Montemayor Casandra 3 ; Mullikin, James C 3 ; Park, Morgan 3 ; Riebow, Nancy L 3 ; Schandler, Karen 3 ; Scharer Chanthra 3 ; Schmidt, Brian 3 ; Sison, Christina 3 ; Sirintorn, Stantripop 3 ; Thomas, James W 3 ; Thomas, Pamela J 3 ; Vemulapalli Meghana 3 ; Young, Alice C 3 ; Burgess, Shawn M 1   VIAFID ORCID Logo 

1  National Human Genome Research Institute, Translational and Functional Genomics Branch, Bethesda, USA (GRID:grid.280128.1) (ISNI:0000 0001 2233 9230) 
2  National Human Genome Research Institute, Cytogenetics and Microscopy Core, Bethesda, USA (GRID:grid.280128.1) (ISNI:0000 0001 2233 9230) 
3  National Institutes of Health, NIH Intramural Sequencing Center, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20573995
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41536-020-0089-0
ProQuest document ID
2382999032
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.