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LHX2 is necessary for the maintenance of optic identity and for the progression of optic morphogenesis
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 33(16)
- Publication Year :
- 2013
-
Abstract
- Eye formation is regulated by a complex network of eye field transcription factors (EFTFs), including LIM-homeodomain gene LHX2. We disrupted LHX2 function at different stages during this process using a conditional knock-out strategy in mice. We find that LHX2 function is required in an ongoing fashion to maintain optic identity across multiple stages, from the formation of the optic vesicle to the differentiation of the neuroretina. At each stage, loss ofLhx2led to upregulation of a set of molecular markers that are normally expressed in the thalamic eminence and in the anterodorsal hypothalamus in a portion of the optic vesicle or retina. Furthermore, the longer LHX2 function was maintained, the further optic morphogenesis progressed. Early loss of function caused profound mispatterning of the entire telencephalic-optic-hypothalamic field, such that the optic vesicle became mispositioned and appeared to arise from the diencephalic-telencephalic boundary. At subsequent stages, loss ofLhx2did not affect optic vesicle position but caused arrest of optic cup formation. IfLhx2was selectively disrupted in the neuroretina from E11.5, the neuroretina showed gross dysmorphology along with aberrant expression of markers specific to the thalamic eminence and anterodorsal hypothalamus. Our findings indicate a continual requirement for LHX2 throughout the early stages of optic development, not only to maintain optic identity by suppressing alternative fates but also to mediate multiple steps of optic morphogenesis. These findings provide new insight into the anophthalmic phenotype of theLhx2mutant and reveal novel roles for this transcription factor in eye development.
- Subjects :
- RNA, Untranslated
genetic structures
PAX6 Transcription Factor
Organogenesis
LIM-Homeodomain Proteins
Morphogenesis
Mice, Transgenic
Nerve Tissue Proteins
Biology
Visual system
Optic cup (anatomical)
Retina
Article
Mice
medicine
Animals
Paired Box Transcription Factors
Visual Pathways
Eye Proteins
Transcription factor
Loss function
Body Patterning
Oligonucleotide Array Sequence Analysis
Homeodomain Proteins
General Neuroscience
Gene Expression Profiling
Age Factors
Gene Expression Regulation, Developmental
Proteins
Optic vesicle
Embryo, Mammalian
Molecular biology
eye diseases
Cell biology
DNA-Binding Proteins
Mice, Inbred C57BL
Repressor Proteins
Tamoxifen
medicine.anatomical_structure
embryonic structures
Mutation
Eye development
sense organs
Transcription Factors
Subjects
Details
- ISSN :
- 15292401
- Volume :
- 33
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....b3e0e3e42470ecc8141c571ce546d631