Mosmo Is Required for Zebrafish Craniofacial Formation
Open Access
- 22 October 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
Hedgehog (Hh) signaling is a highly regulated molecular pathway implicated in many developmental and homeostatic events. Mutations in genes encoding primary components or regulators of the pathway cause an array of congenital malformations or postnatal pathologies, the extent of which is not yet fully defined. Mosmo (Modulator of Smoothened) is a modulator of the Hh pathway, which encodes a membrane tetraspan protein. Studies in cell lines have shown that Mosmo promotes the internalization and degradation of the Hh signaling transducer Smoothened (Smo), thereby down-modulating pathway activation. Whether this modulation is essential for vertebrate embryonic development remains poorly explored. Here, we have addressed this question and show that in zebrafish embryos, the two mosmo paralogs, mosmoa and mosmob, are expressed in the head mesenchyme and along the entire ventral neural tube. At the cellular level, Mosmoa localizes at the plasma membrane, cytoplasmic vesicles and primary cilium in both zebrafish and chick embryos. CRISPR/Cas9 mediated inactivation of both mosmoa and mosmob in zebrafish causes frontonasal hypoplasia and craniofacial skeleton defects, which become evident in the adult fish. We thus suggest that MOSMO is a candidate to explain uncharacterized forms of human congenital craniofacial malformations, such as those present in the 16p12.1 chromosomal deletion syndrome encompassing the MOSMO locus.Funding Information
- Ministerio de Economía, Industria y Competitividad, Gobierno de España (BFU2016-75412-R with FEDER funds)
- Agencia Estatal de Investigación (PID2019-104186RB-I00, RED2018-102553-T, IJCI-2016-27683)
- Fundación Ramón Areces (no ref)
- Comunidad de Madrid (CAM20_CBM_AI_06)
This publication has 49 references indexed in Scilit:
- A review of hedgehog signaling in cranial bone developmentFrontiers in Physiology, 2013
- Mutations in fam20b and xylt1 Reveal That Cartilage Matrix Controls Timing of Endochondral Ossification by Inhibiting Chondrocyte MaturationPLoS Genetics, 2011
- Overlapping Roles and Collective Requirement for the Coreceptors GAS1, CDO, and BOC in SHH Pathway FunctionDevelopmental Cell, 2011
- brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafishDevelopment, 2011
- A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delayNature Genetics, 2010
- Sonic Hedgehog Guides Axons through a Noncanonical, Src-Family-Kinase-Dependent Signaling PathwayNeuron, 2009
- The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse developmentGenes & Development, 2007
- Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skullDevelopment, 2005
- Patterning activities of vertebrate hedgehog proteins in the developing eye and brainCurrent Biology, 1995
- A series of normal stages in the development of the chick embryoDevelopmental Dynamics, 1992