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Otx genes and seizure susceptibility

Homeobox-containing transcription factors crucially regulate the patterning and regionalization of the developing nervous system, as well as the proliferation, survival and differentiation of distinct neuronal populations. Altered expression of these factors markedly impacts the structure and function of the embryonic and adult central nervous system (CNS). In both humans and mice, mutations of homeobox genes have been associated to severe syndromes characterized by developmental CNS defects, which often lead to the occurrence of seizures in the adult life. Among homeobox genes, Otx genes ( Otx1 and Otx2) are crucially involved in brain regionalization. Our previous work showed that mice lacking Otx1 present cerebral cortex defects and develop epilepsy, whereas mice with conditional deletion or overexpression of Otx2 show profound alterations in midbrain-to-forebrain circuits, which are accompanied by an abnormal response to experimentally-induced seizures. In this brief review, we highlight and discuss the major findings suppporting the role of Otx genes in sculpting midbrain and forebrain circuits involved in epileptogenesis.