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.

本仓库包含与下述研究相关的原始、中间及最终补充数据：

内质网应激将嗅觉受体基因的随机选择转化为刻板的轴突导向程序

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, 和 Stavros Lomvardas1,7,8

1美国纽约州纽约市哥伦比亚大学莫蒂默·B·朱克曼心智、脑与行为研究所，邮编10027
2美国纽约州纽约市哥伦比亚大学瓦格洛斯内外科学院医学科学家培训项目，邮编10032
3美国纽约州纽约市哥伦比亚大学欧文医学中心细胞、分子与生物医学研究综合项目，邮编10032
4美国马里兰州贝塞斯达市国立卫生研究院国立神经疾病与中风研究所发育可塑性研究室，邮编20892
5美国加利福尼亚州伯克利市加州大学伯克利分校米勒基础科学研究所
6美国纽约州纽约市巴纳德学院，邮编10025
7美国纽约州纽约市哥伦比亚大学欧文医学中心生物化学与分子生物物理学系，邮编10032
8美国纽约州纽约市哥伦比亚大学欧文医学中心神经科学系，邮编10032

摘要：
嗅觉感觉神经元（OSNs）将超过1000个嗅觉受体（OR）基因中随机选择的一个转化为嗅觉球内OR特异性嗅小球的精确且刻板的轴突靶向。本文中，我们发现未折叠蛋白反应（UPR）的PERK分支既调控相似轴突的嗅小球聚集，也调控其投射的特异性。OR蛋白序列的细微差异导致OSN发育过程中内质网（ER）应激的不同模式，将OR身份转化为独特的基因表达特征。我们鉴定出转录因子Ddit3作为PERK信号通路的关键效应因子，它将OR依赖的ER应激模式映射到轴突导向和细胞黏附基因的转录调控，指导靶向精度。我们的结果将UPR已知的功能从保护细胞免受错误折叠蛋白影响的质量控制通路，扩展为感知细胞身份、解读生理状态以指导轴突连接的传感器。

有关数据集组织的代码及额外信息，请参见https://github.com/hshayya/2022_Shayya_UPR_Guidance。