Six3 regulates optic nerve development via multiple mechanisms
| Autor: | Tehila T. Azar, Zohar Ben-Moshe Livne, Seok-Hyung Kim, Adi Inbal, Ariel Rubinstein, Anat Samuel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
genetic structures Optic chiasm Nerve Tissue Proteins Biology Article 03 medical and health sciences 0302 clinical medicine Optic Nerve Diseases medicine Animals Optic stalk Eye Abnormalities Eye Proteins Zebrafish Homeodomain Proteins Retina Optic nerve hypoplasia Multidisciplinary Gene Expression Regulation Developmental Anatomy medicine.disease eye diseases 030104 developmental biology medicine.anatomical_structure Retinal ganglion cell Optic Chiasm Eye development Optic nerve Axon guidance sense organs Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep20267 |
| Popis: | Malformations of the optic nerve lead to reduced vision or even blindness. During optic nerve development, retinal ganglion cell (RGC) axons navigate across the retina, exit the eye to the optic stalk (OS) and cross the diencephalon midline at the optic chiasm en route to their brain targets. Many signalling molecules have been implicated in guiding various steps of optic nerve pathfinding, however much less is known about transcription factors regulating this process. Here we show that in zebrafish, reduced function of transcription factor Six3 results in optic nerve hypoplasia and a wide repertoire of RGC axon pathfinding errors. These abnormalities are caused by multiple mechanisms, including abnormal eye and OS patterning and morphogenesis, abnormal expression of signalling molecules both in RGCs and in their environment and anatomical deficiency in the diencephalic preoptic area, where the optic chiasm normally forms. Our findings reveal new roles for Six3 in eye development and are consistent with known phenotypes of reduced SIX3 function in humans. Hence, the new zebrafish model for Six3 loss of function furthers our understanding of the mechanisms governing optic nerve development and Six3-mediated eye and forebrain malformations. |
| Databáze: | OpenAIRE |
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