TY - JOUR
T1 - The role of Pax6 in brain development and its impact on pathogenesis of autism spectrum disorder
AU - Kikkawa, Takako
AU - Casingal, Cristine R.
AU - Chun, Seung Hee
AU - Shinohara, Hiroshi
AU - Hiraoka, Kotaro
AU - Osumi, Noriko
N1 - Funding Information:
We thank Drs. Takeo Yoshikawa, Takeo Kubota, and Takeshi Sakurai for valuable suggestions and for critically reading our original manuscript. We also thank Dr. Takeshi Obayashi for technical advice on the meta-analyses. The Pax6 and FoxP2 double-immunostaining image in the cerebellum was kindly provided by Dr. Taku Sugiyama. This work was supported by MEXT Grant-in-Aid for Scientific Research on Innovative Areas (#16H06530) to N.O. and JSPS KAKENHI (#16K20902) to T.K. This work was also supported by Financial Support for English Editing of International Research Papers in Tohoku University Center for Gender Equality Promotion.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2019/2/15
Y1 - 2019/2/15
N2 - Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell–cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.
AB - Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell–cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases.
KW - Autism
KW - Pax6
KW - Transcriptional regulation
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U2 - 10.1016/j.brainres.2018.02.041
DO - 10.1016/j.brainres.2018.02.041
M3 - Review article
C2 - 29499177
AN - SCOPUS:85042853892
SN - 0006-8993
VL - 1705
SP - 95
EP - 103
JO - Brain Research
JF - Brain Research
ER -