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bioRxiv · 10.1101/678417

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

Pei, W.·Xu, L.·Chen, Z.·Slevin, C. C.·Pettie, K. P.·Wincovitch, S.·NISC Comparative Sequencing Program,·Burgess, S. M.
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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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Pei, W., Xu, L., Chen, Z., Slevin, C. C., Pettie, K. P., Wincovitch, S., NISC Comparative Sequencing Program,, Burgess, S. M.. 2019-06-21. A subset of SMN complex members have a specific role in tissue regeneration via ERBB pathway-mediated proliferation. https://doi.org/10.1101/678417

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