4.7 Review

ERK/MAPK signalling in the developing brain: Perturbations and consequences

Journal

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
Volume 131, Issue -, Pages 792-805

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2021.10.009

Keywords

Brain development; ERK; MAPK; Neural progenitors; RAF family; Neurodevelopmental disorders

Funding

  1. International Brain Research Organization (IBRO)
  2. International Society of Neuro-chemistry (ISN)

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The ERK/MAPK signaling pathway plays a crucial role in neurodevelopment, particularly in the development of neural progenitor cells and the proper formation of the nervous system. It is associated with various neurodevelopmental disorders, highlighting its significance in understanding the pathology of these disorders and identifying potential novel therapeutic targets.
The extracellular regulated kinase/microtubule-associated protein kinase (ERK/MAPK) signalling pathway transduces signals that cause an alteration in the ongoing metabolic pathways and modifies gene expression patterns; thus, influencing cellular behaviour. ERK/MAPK signalling is essential for the proper development of the nervous system from neural progenitor cells derived from the embryonic mesoderm. Several signalling molecules that regulate the well-coordinated process of neurodevelopment transduce developmental information through the ERK/MAPK signalling pathway. The ERK/MAPK is a potential novel therapeutic target in several neurodevelopmental disorders, however, despite years of study, there is still significant uncertainty about the exact mechanism by which the ERK/MAPK signalling pathway elicits specific responses in neurodevelopment. Here, we will review the evidence highlighting the role of ERK/MAPK signalling in neurodevelopment. We will also discuss the structural implication and behavioural deficits associated with perturbed ERK/MAPK signalling pathway in cortical development, whilst examining its contribution to the neuropathology of several neurodevelopmental disorders, such as Autism Spectrum Disorder, Schizophrenia, Fragile X, and Attention Deficit Hyperactive Disorder.

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