University Of Tasmania
155655 - Understanding the impact of ZBTB18 missense variation on transcription factor (1).pdf (1.71 MB)

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

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journal contribution
posted on 2023-05-21, 16:52 authored by Heng, JIT, Viti, L, Pugh, K, Owen MarshallOwen Marshall, Agostino, M
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.


National Health & Medical Research Council


Publication title

Journal of neurochemistry








Menzies Institute for Medical Research



Place of publication


Rights statement

© 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Socio-economic Objectives

Expanding knowledge in the health sciences