Otx2, short for orthodenticle homeobox 2, is a member of a highly conserved family of bicoid-like homeodomain transcription factors. It is crucial for the regulation of cerebellar development and early brain development, playing a pivotal role in the specification of neuroectoderm destined to become fore-midbrain [4,5].

In mice, early life stress increases susceptibility to adult social defeat stress, leading to long-lasting transcriptional alterations in the ventral tegmental area (VTA). Transient juvenile knockdown of Otx2 in VTA mimics early life stress by increasing stress susceptibility, while its overexpression reverses these effects, indicating Otx2 as an upstream mediator of these enduring effects [1]. In liver regeneration, MDIG-mediated H3K9me3 demethylation activates Otx2, which then upregulates Myc, facilitating liver regeneration. Genetic MDIG deficiency leads to reduced chromatin accessibility of the Otx2 locus, impairing liver regeneration [3].

In conclusion, Otx2 is essential for various biological processes such as brain development, stress response, and liver regeneration. The use of gene knockout models in mice has been instrumental in revealing its role in these processes. Understanding Otx2 may provide insights into related diseases, including depression-like states and medulloblastoma, where Otx2 has been implicated in proliferation and progression [1,2].