Project description:We observed that the deletion of Anp32b led to severe defects in ocular development, such as anophthalmia and microphthalmia. Moreover, Anp32b was highly expressed in the lens, and Anp32b−/− embryos with microphthalmia typically exhibited severely impaired lens development. Mechanistically, ANP32B directly interacted with paired box protein 6 (PAX6), a master transcriptional regulator of ocular development, and enhanced its transcriptional activity. In line with these findings, overexpression of PAX6 partially but significantly reversed the inhibition of proliferation observed in ANP32B knockdown cells. Collectively, our findings reveal that ANP32B-deficiency suppresses ocular development by repression of PAX6 and identify ANP32B as a viable therapeutic target for ocular developmental defects.
Project description:The homeobox-containing transcription factor PAX6 is a key regulator of eye development. Pathogenic heterozygous PAX6 variants lead to variable ocular phenotypes. Missense variants are often associated with milder ocular conditions, although variants in the DNA-binding paired domain which alter target binding lead to severe ocular phenotypes including bilateral microphthalmia, similar to SOX2 anophthalmia syndrome. However, the variant-specific pathway disruption resulting in phenotypic heterogeneity is not well understood.
Project description:The homeobox-containing transcription factor PAX6 is a key regulator of eye development. Pathogenic heterozygous PAX6 variants lead to variable ocular phenotypes. Missense variants are often associated with milder ocular conditions, although variants in the DNA-binding paired domain which alter target binding lead to severe ocular phenotypes including bilateral microphthalmia, similar to SOX2 anophthalmia syndrome. However, the variant-specific pathway disruption resulting in phenotypic heterogeneity is not well understood.