2022_Shayya_UPR_Guidance
Description
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.
Files
Steps to reproduce
Please see https://github.com/hshayya/2022_Shayya_UPR_Guidance for code and additional information on organization of the dataset. Each zip file uploaded here contains all raw/intermediate/final supplementary data associated with that folder on github. Please download and unzip the relevant file(s) for the portions of the code you wish to replicate.