Boc and Gas1 each form distinct Shh receptor complexes with Ptch1 and are required for Shh-mediated cell proliferation

Copyright © 2011 Elsevier Inc. All rights reserved..

Hedgehog (Hh) proteins regulate important developmental processes, including cell proliferation and differentiation. Although Patched acts as the main Hh receptor in Drosophila, Hh signaling absolutely requires the additional Hh-binding proteins Ihog and Boi. Here we show that, unexpectedly, cerebellar granule neuron progenitors (CGNPs) lacking Boc and Cdon, the vertebrate orthologs of Ihog and Boi, still proliferate in response to Hh. This is because in their absence, Gas1, an Hh-binding protein not present in Drosophila, mediates Hh signaling. Consistently, only CGNPs lacking all three molecules-Boc, Cdon, and Gas1-have a complete loss of Hh-dependent proliferation. In a complementary manner, we find that a mutated Hh ligand that binds Patched1 but not Boc, Cdon, or Gas1 cannot activate Hh signaling. Together, this demonstrates an absolute requirement for Boc, Cdon, and Gas1 in Hh signaling and reveals a distinct requirement for ligand-binding components that distinguishes the vertebrate and invertebrate Hh receptor systems.

Medienart:

E-Artikel

Erscheinungsjahr:

2011

Erschienen:

2011

Enthalten in:

Zur Gesamtaufnahme - volume:20

Enthalten in:

Developmental cell - 20(2011), 6 vom: 14. Juni, Seite 788-801

Sprache:

Englisch

Beteiligte Personen:

Izzi, Luisa [VerfasserIn]
Lévesque, Martin [VerfasserIn]
Morin, Steves [VerfasserIn]
Laniel, Dominique [VerfasserIn]
Wilkes, Brian C [VerfasserIn]
Mille, Frédéric [VerfasserIn]
Krauss, Robert S [VerfasserIn]
McMahon, Andrew P [VerfasserIn]
Allen, Benjamin L [VerfasserIn]
Charron, Frédéric [VerfasserIn]

Links:

Volltext

Themen:

Boc protein, mouse
Cdon protein, mouse
Cell Adhesion Molecules
Cell Cycle Proteins
GPI-Linked Proteins
Gas1 protein, mouse
Hedgehog Proteins
Immunoglobulin G
Journal Article
Patched Receptors
Patched-1 Receptor
Ptch1 protein, mouse
Receptors, Cell Surface
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Shh protein, mouse

Anmerkungen:

Date Completed 16.08.2011

Date Revised 20.10.2021

published: Print

Citation Status MEDLINE

doi:

10.1016/j.devcel.2011.04.017

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM209083549