The homeobox gene Otx2 in development and disease

•The homeobox gene Otx2 is essential for forebrain and craniofacial development.•In the eye, Otx2 is crucial for photoreceptors formation and maintenance.•In the visual cortex, the homeoprotein Otx2 appears to modulate postnatal plasticity.•In human, OTX2 mutations are associated with microphthalmia and brain abnormalities.•Several studies have pointed out an oncogenic role for OTX2 in medulloblastoma.

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 is required after birth for bipolar cells terminal maturation. Otx2 expression is maintained in the differentiated retina wherein the gene is critical for the outer retina maintenance. In the visual cortex, the gene modulates the neuronal plasticity through a paracrine mechanism. OTX2 heterozygous mutations in humans have been linked to severe ocular malformations associated with brain abnormalities and pituitary dysfunction. Recent studies have also established the OTX2 gene as an oncogene for medulloblastoma, a malignant brain tumour originating in the cerebellum.