The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development

Hedgehog (Hh) signaling is critical for patterning and growth during mammalian embryogenesis. Transcriptional profiling identified Growth-arrest-specific 1 (Gas1) as a general negative target of Shh signaling. Data presented here define Gas1 as a novel positive component of the Shh signaling cascade. Removal of Gas1 results in a Shh dose-dependent loss of cell identities in the ventral neural tube and facial and skeletal defects, also consistent with reduced Shh signaling. In contrast, ectopic Gas1 expression results in Shh-dependent cell-autonomous promotion of ventral cell identities. These properties mirror those of Cdo, an unrelated, cell surface Shh-binding protein. We show that Gas1 and Cdo cooperate to promote Shh signaling during neural tube patterning, craniofacial, and vertebral development. Overall, these data support a new paradigm in Shh signaling whereby positively acting ligand-binding components, which are initially expressed in responding tissues to promote signaling, are then down-regulated by active Hh signaling, thereby modulating responses to ligand input.

Medienart:

Artikel

Erscheinungsjahr:

2007

Erschienen:

2007

Enthalten in:

Zur Gesamtaufnahme - volume:21

Enthalten in:

Genes & development - 21(2007), 10 vom: 15. Mai, Seite 1244-57

Sprache:

Englisch

Beteiligte Personen:

Allen, Benjamin L [VerfasserIn]
Tenzen, Toyoaki [VerfasserIn]
McMahon, Andrew P [VerfasserIn]

Themen:

Cdon protein, mouse
Cell Adhesion Molecules
Cell Cycle Proteins
DNA Primers
GPI-Linked Proteins
Gas1 protein, mouse
Hedgehog Proteins
Journal Article
Membrane Proteins
RNA, Small Interfering
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Shh protein, mouse

Anmerkungen:

Date Completed 02.01.2008

Date Revised 13.11.2018

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM17031197X