The transcription factor orthodenticle homeobox 2 (OTX2) has been implicated in the pathogenesis of medulloblastoma, as it is often highly expressed and sometimes amplified in these tumors. Little is known of the downstream pathways regulated by OTX2. We therefore generated MED8A and DAOY medulloblastoma cell lines with doxycycline-inducible OTX2 expression. In both cell lines, OTX2 inhibited p...

Studying the development of mesodiencephalic dopaminergic (mdDA) neurons provides an important basis for better understanding dopamine-associated brain functions and disorders and is critical for establishing cell replacement therapy for Parkinson's disease. The transcription factors Otx2 and Lmx1b play a key role in the development of mdDA neurons. However, little is known about the genes down...

The Otx2 gene encodes a transcription factor essential for the normal development of brain, cerebellum, pineal gland, and eye. In the retina, Otx2 has essential functions from early embryogenesis to adulthood. As soon as the optic vesicle is formed, the gene is required for retinal pigment epithelium specification. Otx2 is also a key regulator of photoreceptor genesis and differentiation, and i...

The Otx2 gene, containing a highly conserved paired-type homeobox, plays a pivotal role in the development of the rostral head throughout vertebrates. Precise regulation of the temporal and spatial expression of Otx2 is likely to be crucial for proper head specification. However, regulatory mechanisms of Otx2 expression remain largely unknown. In this study, the Otx2 genome of the puffer fish F...

We previously showed that otx2 activates ectopic formation of the Xenopus cement gland only in ventrolateral ectoderm, defining a region of the embryo permissive for cement gland formation. In this paper, we explore the molecular identity of this permissive area. One candidate permissive factor is BMP4, whose putative graded inhibition by factors such as noggin has been proposed to activate bot...

PURPOSE Development of the retinal pigment epithelium (RPE) is controlled by intrinsic and extrinsic regulators including orthodenticle homeobox 2 (Otx2) and the Wnt/β-catenin pathway, respectively. Otx2 and β-catenin are necessary for the expression of the RPE key regulator microphthalmia-associated transcription factor (Mitf); however, neither factor is sufficient to promote Mitf expression i...

To better understand the genetic basis of medulloblastoma development, we sought genomic amplifications and deletions in these tumors using digital karyotyping in combination with expression analysis. Five medulloblastoma genomes were karyotyped by sequencing an average of 195,745 genomic DNA tags for each analysis. Tags were tallied at unique positions and mapped to the human genome to determi...

OTX2 is a homeodomain transcription factor that is necessary for normal head development in mouse and man. Heterozygosity for loss-of-function alleles causes an incompletely penetrant, haploinsufficiency disorder. Affected individuals exhibit a spectrum of features that range from developmental defects in eye and/or pituitary development to acephaly. To investigate the mechanism underlying the ...

Plasticity in the visual cerebral cortex is regulated by the internalization of Otx2 homeoprotein into parvalbumin neurons in cortical layers II/III and IV. However the locus is not active in these neurons and the protein is imported from Otx2 external sources, including the choroid plexus. Because Otx1 and Otx2 may have redundant functions, we wanted to verify if part of the staining in parval...

Dissociated primary cultures from rat telencephalon at different developmental stages were used to study the effect of basic fibroblast growth factor (FGF2) on Otx2, Dlx1, and Emx1, three homeobox genes expressed in different regions of the developing mammalian forebrain. At embryonic day (E)13.5. the regional pattern of expression of Otx1, Otx2, Dlx1, Dlx2, Dlx5, and Emx1 is maintained in prim...