Preview

PDF (Fully published version) Pending copyright assessment - Request a copy 2Mb

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 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
Downloads:	0