Augmented BMP signaling commits cranial neural crest cells to a chondrogenic fate by suppressing autophagic β-catenin degradation.

Activin Receptors, Type I / genetics Animals Bone Morphogenetic Proteins / metabolism Chondrogenesis Mechanistic Target of Rapamycin Complex 1 / metabolism Mice Myositis Ossificans Neural Crest / metabolism Osteogenesis Proteolysis Signal Transduction Skull / metabolism beta Catenin / metabolism

Journal

Science signaling
ISSN: 1937-9145
Titre abrégé: Sci Signal
Pays: United States
ID NLM: 101465400

Informations de publication

Date de publication:
12 01 2021
Historique:
entrez: 13 1 2021
pubmed: 14 1 2021
medline: 6 11 2021
Statut: epublish

Résumé

Cranial neural crest cells (CNCCs) are a population of multipotent stem cells that give rise to craniofacial bone and cartilage during development. Bone morphogenetic protein (BMP) signaling and autophagy have been individually implicated in stem cell homeostasis. Mutations that cause constitutive activation of the BMP type I receptor ACVR1 cause the congenital disorder fibrodysplasia ossificans progressiva (FOP), which is characterized by ectopic cartilage and bone in connective tissues in the trunk and sometimes includes ectopic craniofacial bones. Here, we showed that enhanced BMP signaling through the constitutively activated ACVR1 (ca-ACVR1) in CNCCs in mice induced ectopic cartilage formation in the craniofacial region through an autophagy-dependent mechanism. Enhanced BMP signaling suppressed autophagy by activating mTORC1, thus blocking the autophagic degradation of β-catenin, which, in turn, caused CNCCs to adopt a chondrogenic identity. Transient blockade of mTORC1, reactivation of autophagy, or suppression of Wnt-β-catenin signaling reduced ectopic cartilages in ca

Identifiants

DOI: 10.1126/scisignal.aaz9368 PMID: 33436499 PMC: PMC7936468
pubmed: 33436499
pii: 14/665/eaaz9368
doi: 10.1126/scisignal.aaz9368
pmc: PMC7936468
mid: NIHMS1675721
pii:
doi:

Substances chimiques

Bone Morphogenetic Proteins 0
beta Catenin 0
Mechanistic Target of Rapamycin Complex 1 EC 2.7.11.1
Activin Receptors, Type I EC 2.7.11.30
Acvr1 protein, mouse EC 2.7.11.30

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIDCR NIH HHS
ID : R01 DE020843
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE025897
Pays : United States
Organisme : NIDCR NIH HHS
ID : R03 DE027456
Pays : United States

Informations de copyright

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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Auteurs

Jingwen Yang (J)

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
ORCID: 0000-0001-8969-6486

Megumi Kitami (M)

Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX 77030, USA.
Graduate Program in Genes and Development, University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.

Haichun Pan (H)

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.

Masako Toda Nakamura (MT)

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-1588-5388

Honghao Zhang (H)

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-2338-6992

Fei Liu (F)

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-2646-3009

Lingxin Zhu (L)

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
ORCID: 0000-0002-6762-7882

Yoshihiro Komatsu (Y)

Department of Pediatrics, University of Texas Medical School at Houston, Houston, TX 77030, USA. yoshihiro.komatsu@uth.tmc.edu mishina@umich.edu.
Graduate Program in Genes and Development, University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.

Yuji Mishina (Y)

Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA. yoshihiro.komatsu@uth.tmc.edu mishina@umich.edu.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs TGF-bêta › Récepteur activine › Récepteur activine, type 1 › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Eucaryotes › Animaux › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la superfamille du TGF bêta › Protéines morphogénétiques osseuses › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Développement locomoteur › Chondrogenèse › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Complexe-1 cible mécanistique de la rapamycine › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Maladies ostéomusculaires › Myosite ossifiante › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Structures de l'embryon › Crête neurale › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Développement locomoteur › Biominéralisation › Développement osseux › Ostéogenèse › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Métabolisme › Protéolyse › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Appareil locomoteur › Squelette › Crâne › Augmented BMP signaling commits cranial neural...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Augmented BMP signaling commits cranial neural...