The hedgehog co-receptor BOC differentially regulates SHH signaling during craniofacial development

© 2020. Published by The Company of Biologists Ltd..

The Hedgehog (HH) pathway controls multiple aspects of craniofacial development. HH ligands signal through the canonical receptor PTCH1, and three co-receptors: GAS1, CDON and BOC. Together, these co-receptors are required during embryogenesis to mediate proper HH signaling. Here, we investigated the individual and combined contributions of GAS1, CDON and BOC to HH-dependent mammalian craniofacial development. Notably, individual deletion of either Gas1 or Cdon results in variable holoprosencephaly phenotypes in mice, even on a congenic background. In contrast, we find that Boc deletion results in facial widening that correlates with increased HH target gene expression. In addition, Boc deletion in a Gas1 null background partially ameliorates the craniofacial defects observed in Gas1 single mutants; a phenotype that persists over developmental time, resulting in significant improvements to a subset of craniofacial structures. This contrasts with HH-dependent phenotypes in other tissues that significantly worsen following combined deletion of Gas1 and Boc Together, these data indicate that BOC acts as a multi-functional regulator of HH signaling during craniofacial development, alternately promoting or restraining HH pathway activity in a tissue-specific fashion.

Media Type:

Electronic Article

Year of Publication:

2020

Contained In:

Development (Cambridge, England) - Vol. 147, No. 23 (2020)

Language:

English

Contributors:

Echevarría-Andino, Martha L
Allen, Benjamin L

Links:

Volltext

Keywords:

Animals
BOC
Boc protein, mouse
CDON
Cdon protein, mouse
Cell Adhesion Molecules
Cell Cycle Proteins
Craniofacial Abnormalities
Craniofacial development
Embryonic Development
GAS1
GPI-Linked Proteins
Gas1 protein, mouse
Gene Deletion
Hedgehog
Hedgehog Proteins
Holoprosencephaly
Humans
Immunoglobulin G
Journal Article
Mice
Mouse
Patched-1 Receptor
Ptch1 protein, mouse
Receptors, Cell Surface
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Signal Transduction

Notes:

Date Completed 26.01.2021

Date Revised 26.02.2021

published: Electronic

Citation Status MEDLINE

Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Physical Description:

Online-Ressource

doi:

10.1242/dev.189076

PMID:

33060130

PPN (Catalogue-ID):

NLM317269933