The homeodomain protein, Otx2, is a critical regulator of vertebrate photoreceptor genesis. However, the genetic elements that define the expression of Otx2 during photoreceptor development are unknown. Therefore, we sought to identify an Otx2 enhancer element that functions in photoreceptor development in order to better understand this specification event. Using the technique of electroporati...

Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, contribute to brain morphogenesis. In particular Otx1 null mice are viable and show spontaneous epileptic seizures and abnormalities affecting the dorsal telencephalic cortex. Otx2 null mice die early in development and fail in specification of the rostral neuroectoderm and proper gastrulation. In order to determine ...

The transcription factor Otx2 is expressed throughout the anterior neuroectoderm and is required for the formation of all forebrain- and midbrain-derived structures. The molecular determinants that cooperate with Otx2 to subdivide its expression domain into distinct functional units are, however, poorly understood at present. We show here that the TALE-homeodomain protein Meis2 is expressed in ...

Despite an emerging understanding of the genetic alterations giving rise to various tumors, the mechanisms whereby most oncogenes are overexpressed remain unclear. Here we have utilized an integrated approach of genomewide regulatory element mapping via DNase-seq followed by conventional reporter assays and transcription factor binding site discovery to characterize the transcriptional regulati...

The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, ...

The patterns of the Gbx2, Pax2, Wnt1, and Fgf8 gene expression were analyzed in the chick with respect to the caudal limit of the Otx2 anterior domain, taken as a landmark of the midbrain/hindbrain (MH) boundary. The Gbx2 anterior boundary is always concomitant with the Otx2 posterior boundary. The ring of Wnt1 expression is included within the Otx2 domain and Fgf8 transcripts included within t...

GABAergic and glutamatergic neurons modulate inhibitory and excitatory networks in the CNS, and their impairment may cause neurological and psychiatric disorders. Thus, understanding the molecular mechanisms that control neurotransmitter phenotype and identity of excitatory and inhibitory progenitors has considerable relevance. Here we investigated the consequence of Otx2 (orthodenticle homolog...

Otx2 is expressed in the mesencephalon and prosencephalon, and Gbx2 is expressed in the rhombencephalon around stage 10. Loss-of-function studies of these genes in mice have revealed that Otx2 is indispensable for the development of the anterior brain segment, and that Gbx2 is required for the development of the isthmus. We carried out gain-of-function experiments of these genes in chick embryo...

The superior colliculus (SC), a relay nucleus in the subcortical visual pathways, is implicated in socioemotional behaviors. Homeoprotein Otx2 and β subunit of receptors of platelet-derived growth factor (PDGFR- β ) have been suggested to play an important role in development of the visual system and development and maturation of GABAergic neurons. Although PDGFR- β -knockout (KO) mice displaye...

Purpose Heterozygous mutations in OTX2 have been associated with a range of ocular and pituitary abnormalities. We report a novel heterozygous deletion in OTX2 underlying early-onset retinal dystrophy with atypical maculopathy. Methods Clinical examination included electroretinography and multimodal retinal imaging. Molecular genetic testing was composed of next-generation sequencing of a pan...