Transcription factors in neurodevelopmental and associated psychiatric disorders: A potential convergence for genetic and environmental risk factors

Int J Dev Neurosci. 2021 Nov;81(7):545-578. doi: 10.1002/jdn.10141. Epub 2021 Aug 3.

Abstract

Neurodevelopmental disorders (NDDs) are a heterogeneous and highly prevalent group of psychiatric conditions marked by impairments in the nervous system. Their onset occurs during gestation, and the alterations are observed throughout the postnatal life. Although many genetic and environmental risk factors have been described in this context, the interactions between them challenge the understanding of the pathways associated with NDDs. Transcription factors (TFs)-a group of over 1,600 proteins that can interact with DNA, regulating gene expression through modulation of RNA synthesis-represent a point of convergence for different risk factors. In addition, TFs organize critical processes like angiogenesis, blood-brain barrier formation, myelination, neuronal migration, immune activation, and many others in a time and location-dependent way. In this review, we summarize important TF alterations in NDD and associated disorders, along with specific impairments observed in animal models, and, finally, establish hypotheses to explain how these proteins may be critical mediators in the context of genome-environment interactions.

Keywords: animal model; environment-genome interaction; neurodevelopmental disorders; psychiatric disorders; transcription; transcription factors.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene-Environment Interaction*
  • Humans
  • Mental Disorders / etiology*
  • Mental Disorders / genetics
  • Neurodevelopmental Disorders / etiology*
  • Neurodevelopmental Disorders / genetics
  • Risk Factors
  • Transcription Factors / genetics*

Substances

  • Transcription Factors