PUBLICATION
Six3 regulates optic nerve development via multiple mechanisms
- Authors
- Samuel, A., Rubinstein, A.M., Azar, T.T., Ben-Moshe Livne, Z., Kim, S.H., Inbal, A.
- ID
- ZDB-PUB-160130-6
- Date
- 2016
- Source
- Scientific Reports 6: 20267 (Journal)
- Registered Authors
- Inbal, Adi, Kim, Seok-Hyung
- Keywords
- Axon and dendritic guidance, Developmental neurogenesis
- MeSH Terms
-
- Nerve Tissue Proteins/biosynthesis*
- Nerve Tissue Proteins/genetics
- Homeodomain Proteins/biosynthesis*
- Homeodomain Proteins/genetics
- Zebrafish/embryology*
- Zebrafish/genetics
- Optic Chiasm/cytology
- Optic Chiasm/embryology*
- Optic Nerve Diseases/congenital
- Optic Nerve Diseases/embryology
- Optic Nerve Diseases/genetics
- Eye Abnormalities/embryology
- Eye Abnormalities/genetics
- Gene Expression Regulation, Developmental/physiology*
- Eye Proteins/biosynthesis*
- Eye Proteins/genetics
- Animals
- PubMed
- 26822689 Full text @ Sci. Rep.
Citation
Samuel, A., Rubinstein, A.M., Azar, T.T., Ben-Moshe Livne, Z., Kim, S.H., Inbal, A. (2016) Six3 regulates optic nerve development via multiple mechanisms. Scientific Reports. 6:20267.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping