Shtn1, a retinal ganglion cell (RGC) specific gene, regulates RGC neurite development: Insights from an RGC direct somatic cell reprogramming model

Retinal ganglion cells (RGCs) are the projection neurons of the retina. Proper development of the axon and dendrite of RGCs is the basis for these cells to function as projection neurons to deliver visual information to the brain. The purpose of this study was to investigate the function of a newly identified RGC-specific gene, Shtn1, in neurite development in RGCs. Using IF, we demonstrated that SHTN1 is distinctively expressed in RGCs during the period in which RGCs actively develop and adjust the connections of their neurites with upstream and downstream neurons. Using the iRGC system, we demonstrated that Shtn1 promotes the growth and complexity of neurites, and thus the electrophysiological maturation, of iRGCs. RNA-Seq analyses showed that Shtn1 may also regulate gene expression and neurogenesis in iRGCs. These findings improve our understanding of the molecular machinery governing RGC neurite development, and may help to optimize future RGC regeneration methods. MEFs was infected with lentiviruses overexpressing Ascl1+Brn3b+Islet1 to generate RGC-like neurons (iRGCs), shRNAs were used to knock down Shtn1. Cells were collected 5 days after exogenous gene induciton, and processed for RNA-Seq sequencing.