title: LHX2 is necessary for the maintenance of optic identity and for the progression of optic morphogenesis.
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 of Lhx2 led 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 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 anophthalmic phenotype of the Lhx2 mutant and reveal novel roles for this transcription factor in eye development.
authors.affiliation: Tata Institute of Fundamental Research, Mumbai, India 400005.
authors.forename: Achira
authors.initials: A
authors.lastname: Roy
authors.forename: Jimmy
authors.initials: J
authors.lastname: de Melo
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Chaturvedi
authors.forename: Thuzar
authors.initials: T
authors.lastname: Thein
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cabrera-Socorro
authors.forename: Corinne
authors.initials: C
authors.lastname: Houart
authors.forename: Gundela
authors.initials: G
authors.lastname: Meyer
authors.forename: Seth
authors.initials: S
authors.lastname: Blackshaw
authors.forename: Shubha
authors.initials: S
authors.lastname: Tole
mesh_terms: D000367:Age Factors; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D038081:Organogenesis / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D012097:Repressor Proteins / Q000378:metabolism; D012160:Retina / Q000002:abnormalities / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014795:Visual Pathways / Q000196:embryology / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489784:Lhx2 protein, mouse; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D011506:Proteins; D022661:RNA, Untranslated; D012097:Repressor Proteins; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; D013629:Tamoxifen