Sox11 Is Required to Maintain Proper Levels of Hedgehog Signaling during Vertebrate Ocular Morphogenesis

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Ocular coloboma is a condition in which tissue is missing from a portion of the eye due to its abnormal development. Coloboma is also frequently associated with additional anomalies, including microphthalmia (abnormally small eye) and cataracts. Although some of the genes that cause coloboma have been identified, in the majority of cases the underlying genetic cause has not been determined. One pathway that has been implicated in coloboma is the Hedgehog (Hh) signaling pathway. In this study, we have taken advantage of the ability to titrate levels of gene expression in zebrafish to demonstrate for the first time that the transcription factor Sox11 is required to limit levels of Hedgehog (Hh) signaling during ocular development. We show that in the absence of Sox11, levels of the Sonic Hedgehog (Shh) ligand are greatly elevated, which disrupts the proper patterning of the optic stalk and optic vesicle, resulting in coloboma. We also provide evidence that SOX11 dosage changes or mutations contribute to human coloboma, microphthalmia, and rod photoreceptor dysfunction. Thus, our work establishes a novel link between Sox11 and Hh signaling, and suggests that mutations in SOX11 contribute to pediatric eye disorders such as coloboma.

Vyšlo v časopise: Sox11 Is Required to Maintain Proper Levels of Hedgehog Signaling during Vertebrate Ocular Morphogenesis. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004491
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004491

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