کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5531796 1401815 2017 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cilia-dependent GLI processing in neural crest cells is required for tongue development
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Cilia-dependent GLI processing in neural crest cells is required for tongue development
چکیده انگلیسی


- NCCs and mesodermally-derived muscle precursors contribute to glossal development.
- Increased apoptosis in both NCCs and mesodermally-derived muscle precursors contributes to ciliopathic aglossia.
- Muscle precursors fail to migrate into the tongue anlage of ciliary mutants.
- GLI activator activity is lost in the developing mandible of ciliary mutants.
- Restoration of GLI activator activity can partially rescue glossal development.

Ciliopathies are a class of diseases caused by the loss of a ubiquitous, microtubule-based organelle called a primary cilium. Ciliopathies commonly result in defective development of the craniofacial complex, causing midfacial defects, craniosynostosis, micrognathia and aglossia. Herein, we explored how the conditional loss of primary cilia on neural crest cells (Kif3af/f;Wnt1-Cre) generated aglossia. On a cellular level, our data revealed that aglossia in Kif3af/f;Wnt1-Cre embryos was due to a loss of mesoderm-derived muscle precursors migrating into and surviving in the tongue anlage. To determine the molecular basis for this phenotype, we performed RNA-seq, in situ hybridization, qPCR and Western blot analyses. We found that transduction of the Sonic hedgehog (Shh) pathway, rather than other pathways previously implicated in tongue development, was aberrant in Kif3af/f;Wnt1-Cre embryos. Despite increased production of full-length GLI2 and GLI3 isoforms, previously identified GLI targets important for mandibular and glossal development (Foxf1, Foxf2, Foxd1 and Foxd2) were transcriptionally downregulated in Kif3af/f;Wnt1-Cre embryos. Genetic removal of GLI activator (GLIA) isoforms in neural crest cells recapitulated the aglossia phenotype and downregulated Fox gene expression. Genetic addition of GLIA isoforms in neural crest cells partially rescued the aglossia phenotype and Fox gene expression in Kif3af/f;Wnt1-Cre embryos. Together, our data suggested that glossal development requires primary cilia-dependent GLIA activity in neural crest cells. Furthermore, these data, in conjunction with our previous work, suggested prominence specific roles for GLI isoforms; with development of the frontonasal prominence relying heavily on the repressor isoform and the development of the mandibular prominence/tongue relying heavily on the activator isoform.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Biology - Volume 424, Issue 2, 15 April 2017, Pages 124-137
نویسندگان
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