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Understanding the impact of ZBTB18 missense variation on transcription factor function in neurodevelopment and disease


Heng, JIT and Viti, L and Pugh, K and Marshall, OJ and Agostino, M, Understanding the impact of ZBTB18 missense variation on transcription factor function in neurodevelopment and disease, Journal of neurochemistry, 161, (3) pp. 219-235. ISSN 1471-4159 (2022) [Refereed Article]

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DOI: doi:10.1111/jnc.15572


Mutations to genes that encode DNA-binding transcription factors (TFs) underlie a broad spectrum of human neurodevelopmental disorders. Here, we highlight the pathological mechanisms arising from mutations to TF genes that influence the development of mammalian cerebral cortex neurons. Drawing on recent findings for TF genes including ZBTB18, we discuss how functional missense mutations to such genes confer non-native gene regulatory actions in developing neurons, leading to cell-morphological defects, neuroanatomical abnormalities during foetal brain development and functional impairment. Further, we discuss how missense variation to human TF genes documented in the general population endow quantifiable changes to transcriptional regulation, with potential cell biological effects on the temporal progression of cerebral cortex neuron development and homeostasis. We offer a systematic approach to investigate the functional impact of missense variation in brain TFs and define their direct molecular and cellular actions in foetal neurodevelopment, tissue homeostasis and disease states.

Item Details

Item Type:Refereed Article
Keywords:Transcription factors, population variants, gene regulation, development, brain development
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Cellular nervous system
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Marshall, OJ (Dr Owen Marshall)
ID Code:155655
Year Published:2022
Funding Support:National Health and Medical Research Council (1185220)
Deposited By:Menzies Institute for Medical Research
Deposited On:2023-03-03
Last Modified:2023-03-06

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