LHX2 is necessary for the maintenance of optic identity and for the progression of optic morphogenesis

Achira Roy, Jimmy de Melo, Dhananjay Chaturvedi, Thuzar Thein, Alfredo Cabrera-Socorro, Corinne Houart, Gundela Meyer, Seth Blackshaw, Shubha Tole*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

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. A teach stage, loss ofLhx2ledtoupregulationofasetofmolecular markers that are normally expressed in the thalamic eminence and in the anterodorsal hypothalamusina portion of the optic vesicleorretina. 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 of Lhx2 did not affect optic vesicle position but caused arrest of optic cup formation. If Lhx2 was 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 an ophthalmic phenotype of the Lhx2 mutant and reveal novel roles for this transcription factor in eye development.

Original languageEnglish
Pages (from-to)6877-6884
Number of pages8
JournalJournal of Neuroscience
Volume33
Issue number16
DOIs
Publication statusPublished - 17 Apr 2013

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