Thirty Years’ History since the Discovery of Pax6: From Central Nervous System Development to Neurodevelopmental Disorders

Abstract

Pax6 is a sequence-specific DNA binding transcription factor that positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system (CNS). As indicated by the morphological and functional abnormalities in spontaneous Pax6 mutant rodents, Pax6 plays pivotal roles in various biological processes in the CNS. At the initial stage of CNS development, Pax6 is responsible for brain patterning along the anteroposterior and dorsoventral axes of the telencephalon. Regarding the anteroposterior axis, Pax6 is expressed inversely to Emx2 and Coup-TF1, and Pax6 mutant mice exhibit a rostral shift, resulting in an alteration of the size of certain cortical areas. Pax6 and its downstream genes play important roles in balancing the proliferation and differentiation of neural stem cells. The Pax6 gene was originally identified in mice and humans 30 years ago via genetic analyses of the eye phenotypes. The human PAX6 gene was discovered in patients who suffer from WAGR syndrome (i.e., Wilms tumor, aniridia, genital ridge defects, mental retardation). Mutations of the human PAX6 gene have also been reported to be associated with autism spectrum disorder (ASD) and intellectual disability. Rodents that lack the Pax6 gene exhibit diverse neural phenotypes, which might lead to a better understanding of human pathology and neurodevelopmental disorders. This review describes the expression and function of Pax6 during brain development, and their implications for neuropathology.

Long noncoding RNA MALAT1 inhibition attenuates sepsis‐induced acute lung injury through modulating the miR‐129‐5p/PAX6/ZEB2 axis

“…Paired box gene (PAX6) refers to a sequence‐specific DNA‐binding transcription factor, positively and negatively regulating transcription 18 . A previous study has indicated that miR‐129‐5p directly targets the 3′‐untranslated region (UTR) of PAX6 19 .…”

“…Paired box gene (PAX6) refers to a sequence-specific DNA-binding transcription factor, positively and negatively regulating transcription. 18 A previous study has indicated that miR-129-5p directly targets the 3′-untranslated region (UTR) of PAX6. 19 It is also reported that PAX6 is increased in non-small-cell lung cancer (NSCLC) and directly inhibited by miR-129-5p.…”

Aberrant expression of COL4A1 in age-related cataract and its effect on cell proliferation, apoptosis and gene expression changes

“…Mutations in PLOD1 or PLOD2 are linked with Ehlers-Danlos syndrome type VI in patients [32] , who present ocular similarities to Axenfeld-Rieger anomaly/Axenfeld-Rieger syndrome, particularly glaucoma and microcornea [10,33] . PAX6 gene is reported to influence development of the central nervous system and also has been known as a key regulator of eye development [34] . Pathogenic mutations of PAX6 also have been demonstrated to involve in the congenital cataracts, aniridia, anophthalmia and other multiple ocular defects in human [35] .…”

Knockout of signal peptide peptidase in the eye reduces HSV-1 replication and eye disease in ocularly infected mice

“…Previous studies showed that congenital aniridia (lack of an iris) in humans and murine small eye phenotypes, both arise from homologous defects in Pax6 [56,57]. In mice, the heterozygous Pax6 phenotype is associated with small eye, while Pax6 homozygous mutant mice lack eyes and a nose and die after birth [58]. Pax6 is expressed in the lens, corneal epithelium, retinal neuroepithelium, and olfactory placodes/epithelium [59][60][61][62].…”