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

Abstract

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.