2022_Shayya_UPR_Guidance

This repository contains raw, intermediate and final supplementary data associated with the following study:

ER stress transforms stochastic olfactory receptor gene choice into stereotypic axon guidance programs

Hani J. Shayya1,2,3, Jerome K. Kahiapo1,3, Rachel Duffié1, Katherine S. Lehmann4, Lisa Bashkirova1, Kevin Monahan1, Ryan P. Dalton5, Joanna Gao6, Song Jiao4, Ira Schieren1, Leonardo Belluscio4, and Stavros Lomvardas1,7,8

1Mortimer B. Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY 10027, USA
2Medical Scientist Training Program, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA
3Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA
4Developmental Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892 USA
5The Miller Institute for Basic Research in Science, University of California Berkeley, Berkeley, CA 94720 USA
6Barnard College, New York, NY, 10025 USA
7Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA
8Department of Neuroscience, Columbia University Irving Medical Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA

Abstract:
Olfactory sensory neurons (OSNs) transform the stochastic choice of one out of >1000 olfactory receptor (OR) genes into precise and stereotyped axon targeting of OR-specific glomeruli in the olfactory bulb. Here, we show that the PERK arm of the unfolded protein response (UPR) regulates both the glomerular coalescence of like axons, and the specificity of their projections. Subtle differences in OR protein sequences lead to distinct patterns of endoplasmic reticulum (ER) stress during OSN development, converting OR identity into distinct gene expression signatures. We identify the transcription factor Ddit3 as a key effector of PERK signaling that maps OR-dependent ER stress patterns to the transcriptional regulation of axon guidance and cell adhesion genes, instructing targeting precision. Our results extend the known functions of the UPR from a quality control pathway that protects cells from misfolded proteins, to a sensor of cellular identity that interprets physiological states to direct axon wiring.

Please see https://github.com/hshayya/2022_Shayya_UPR_Guidance for code and additional information on organization of the dataset.