An shRNA-based in vivo retina screen identifies molecules that regulate presynaptic development of rod photoreceptor

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NEI	NEURO-13

Authors

• S.Y. Kim
• C. Park
• M. Brooks
• A. Klingenhoff
• R. Villasmill
• H. Hong
• R. Farriss
• T. Cogliati
• W. Li
• A. Swaroop

Abstract

Brain has a morphological variety of neuronal types. How such diversified neurons develop and specific circuits form among groups of neurons are veiled. Retina is one of CNS structures, but far less complex than brain. Photoreceptors are a specialized neuron type to detect photons and transduce visual inputs. The presynapses of rod and cone photoreceptor called spherule and pedicle, respectively, have specialized ribbon structure in them, which are different from conventional presynapses in brain. Spherule and pedicle, further, exhibit differential morphologies and connections with distinct sets of second-order neurons in the distinct sublaminae of retinal outer plexiform layer (OPL). However, the molecular mechanisms that generate distinct ribbon synapses between spherule and pedicle remain unknown. Here, we report that fate determinant transcription factor (TF) NRL and downstream effectors are critical for spherule morphogenesis. GO analysis of Nrl ChIP-seq and RNA-seq of WT and Nrl-/- retina, and combined in vivo imaging using retinal electroporation of shRNAs revealed the involvement of Nfasc, St8sia1, Pla2g7 and Sntb2 in spherule development. Our data indicate that fate determinate TFs and the cascade effectors control the specific synaptic development of distinct neuron-types.

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