Dataset Information

Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-? signaling.

ABSTRACT: Cranial neural crest cells form much of the facial skeleton, and abnormalities in their development lead to severe birth defects. In a novel zebrafish protein trap screen, we identified an RNA-binding protein, Rbms3, that is transiently expressed in the cytoplasm of condensing neural crest cells within the pharyngeal arches. Morphants for rbms3 displayed reduced proliferation of prechondrogenic crest and significantly altered expression for chondrogenic/osteogenic lineage markers. This phenotype strongly resembles cartilage/crest defects observed in Tgf-?r2:Wnt1-Cre mutants, which suggests a possible link with TGF-? signaling. Consistent with this are the findings that: (a) Rbms3 stabilized a reporter transcript with smad2 3' untranslated region, (b) RNA immunoprecipitation with full-length Rbms3 showed enrichment for smad2/3, and (c) pSmad2 levels were reduced in rbms3 morphants. Overall, these results suggest that Rbms3 posttranscriptionally regulates one of the major pathways that promotes chondrogenesis, the transforming growth factor ? receptor (TGF-?r) pathway.

SUBMITTER: Jayasena CS

PROVIDER: S-EPMC3483135 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-β signaling.

Jayasena Chathurani S CS Bronner Marianne E ME

The Journal of cell biology 20121022 3

Cranial neural crest cells form much of the facial skeleton, and abnormalities in their development lead to severe birth defects. In a novel zebrafish protein trap screen, we identified an RNA-binding protein, Rbms3, that is transiently expressed in the cytoplasm of condensing neural crest cells within the pharyngeal arches. Morphants for rbms3 displayed reduced proliferation of prechondrogenic crest and significantly altered expression for chondrogenic/osteogenic lineage markers. This phenotype ...[more]

PMID: 23091072

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Project description:Much of the bone, cartilage and smooth muscle of the vertebrate face is derived from neural crest (NC) cells. During craniofacial development, the anterior neural ridge (ANR) and olfactory pit (OP) signaling centers are responsible for driving the outgrowth, survival, and differentiation of NC populated facial prominences, primarily via FGF. While much is known about the functional importance of signaling centers, relatively little is understood of how these signaling centers are made and maintained. In this report we describe a dramatic craniofacial malformation in mice mutant for the zinc finger transcription factor gene Sp8. At E14.5 they show facial prominences that are reduced in size and underdeveloped, giving an almost faceless phenotype. At later times they show severe midline defects, excencephaly, hyperterlorism, cleft palate, and a striking loss of many NC and paraxial mesoderm derived cranial bones. Sp8 expression was primarily restricted to the ANR and OP regions during craniofacial development. Analysis of an extensive series of conditional Sp8 mutants confirmed the critical role of Sp8 in signaling centers, and not directly in the NC and paraxial mesoderm cells. The NC cells of the Sp8 mutants showed increased levels of apoptosis and decreased cell proliferation, thereby explaining the reduced sizes of the facial prominences. Perturbed gene expression in the Sp8 mutants was examined by laser capture microdissection coupled with microarrays, as well as in situ hybridization and immunostaining. The most dramatic differences included striking reductions in Fgf8 and Fgf17 expression in the ANR and OP signaling centers. We were also able to achieve genetic and pharmaceutical partial rescue of the Sp8 mutant phenotype by reducing Sonic Hedgehog (SHH) signaling. These results show that Sp8 primarily functions to promote Fgf expression in the ANR and OP signaling centers that drive the survival, proliferation, and differentiation of the NC and paraxial mesoderm that make the face.

Dataset Information

Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-? signaling.

Publications

Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-β signaling.

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