A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation

Wuhong Pei; Lisha Xu; Zelin Chen; Claire C. Slevin; Kade P. Pettie; Stephen Wincovitch; NISC Comparative Sequencing Program; Beatrice B. Barnabas; Sean Black; Gerard G. Bouffard; Shelise Y. Brooks; Holly Coleman; Lyudmila Dekhtyar; Xiaobin Guan; Joel Han; Shi-ling Ho; Richelle Legaspi; Quino L. Maduro; Catherine A. Masiello; Jennifer C. McDowell; Casandra Montemayor; James C. Mullikin; Morgan Park; Nancy L. Riebow; Karen Schandler; Chanthra Scharer; Brian Schmidt; Christina Sison; Sirintorn Stantripop; James W. Thomas

doi:10.1038/s41536-020-0089-0

Geneticsnpj Regenerative MedicineMar 25, 2020

Peer-reviewed journal article

A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation

Wuhong Pei, Lisha Xu iD, Zelin Chen iD, Claire C. Slevin iD, Kade P. Pettie iD, Stephen Wincovitch iD, NISC Comparative Sequencing Program, Beatrice B. Barnabas, Sean Black, Gerard G. Bouffard iD, Shelise Y. Brooks iD, Holly Coleman iD, Lyudmila Dekhtyar, Xiaobin Guan, Joel Han, Shi-ling Ho, Richelle Legaspi, Quino L. Maduro, Catherine A. Masiello, Jennifer C. McDowell, Casandra Montemayor, James C. Mullikin iD, Morgan Park, Nancy L. Riebow, Karen Schandler, , Shawn Michael Burgess iD

Abstract

Spinal Muscular Atrophy (SMA) is the most common genetic disease in childhood. SMA is generally caused by mutations in 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 and miRNA-Seq analyses reveal 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.

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