Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Gpr161 ciliary pools prevent hedgehog pathway hyperactivation phenotypes specifically from lack of Gli transcriptional repression

Sun-Hee Hwang, Bandarigoda N. Somatilaka, Kevin White, View ORCID ProfileSaikat Mukhopadhyay
doi: https://doi.org/10.1101/2021.01.07.425654
Sun-Hee Hwang
1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bandarigoda N. Somatilaka
1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
2Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin White
1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Saikat Mukhopadhyay
1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, 75390
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Saikat Mukhopadhyay
  • For correspondence: Saikat.Mukhopadhyay@utsouthwestern.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The primary cilium localized G-protein-coupled receptor Gpr161 represses hedgehog pathway via cAMP signaling in multiple tissues. However, whether Gpr161 functions exclusively from inside cilia is unclear. Here, we generated ciliary localization-defective but cAMP signaling-competent Gpr161mut1 knock-in mice. We uncovered distinctive roles for subcellular Gpr161 pools, contingent upon dependence of the morpho-phenotypic spectrum on downstream Gli transcriptional regulators. Compared to Gpr161 knockout, gene dosage of the Gpr161mut1 allele caused delayed embryonic lethality, reduced upregulation of hedgehog targets and intermediate Gli3 repressor levels. Unlike Gpr161 knockout with aberrant ventral progenitor expansion in neural tube, extraciliary Gpr161 pools in Gpr161mut1 prevented Gli2 activator-mediated ventralization. However, limb buds and midfacial tissues that require Gli repressor for morphogenesis, showed polydactyly and midface widening in Gpr161mut1 from hyperactivation. Thus, Gpr161 ciliary and extraciliary pools functioned as rheostats preventing gradations of hedgehog pathway hyperactivation. Ciliary Gpr161 pools prevented tissue-specific phenotypes dependent specifically on reduced Gli repressor thresholds.

  • Cilia
  • hedgehog
  • cAMP
  • Gpr161
  • Gli repressor
  • neural tube
  • craniofacial
  • limb bud
  • polydactyly
  • morphogenesis

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted January 07, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Gpr161 ciliary pools prevent hedgehog pathway hyperactivation phenotypes specifically from lack of Gli transcriptional repression
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Gpr161 ciliary pools prevent hedgehog pathway hyperactivation phenotypes specifically from lack of Gli transcriptional repression
Sun-Hee Hwang, Bandarigoda N. Somatilaka, Kevin White, Saikat Mukhopadhyay
bioRxiv 2021.01.07.425654; doi: https://doi.org/10.1101/2021.01.07.425654
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Gpr161 ciliary pools prevent hedgehog pathway hyperactivation phenotypes specifically from lack of Gli transcriptional repression
Sun-Hee Hwang, Bandarigoda N. Somatilaka, Kevin White, Saikat Mukhopadhyay
bioRxiv 2021.01.07.425654; doi: https://doi.org/10.1101/2021.01.07.425654

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Developmental Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4078)
  • Biochemistry (8750)
  • Bioengineering (6467)
  • Bioinformatics (23314)
  • Biophysics (11719)
  • Cancer Biology (9133)
  • Cell Biology (13227)
  • Clinical Trials (138)
  • Developmental Biology (7403)
  • Ecology (11360)
  • Epidemiology (2066)
  • Evolutionary Biology (15076)
  • Genetics (10390)
  • Genomics (14000)
  • Immunology (9109)
  • Microbiology (22025)
  • Molecular Biology (8772)
  • Neuroscience (47312)
  • Paleontology (350)
  • Pathology (1418)
  • Pharmacology and Toxicology (2480)
  • Physiology (3701)
  • Plant Biology (8043)
  • Scientific Communication and Education (1427)
  • Synthetic Biology (2206)
  • Systems Biology (6009)
  • Zoology (1247)