The neurodevelopmental implications of PI3K signaling.

ABSTRACT

Our understanding of the mechanisms involved in the formation of the complex arrangement of neurons and their interconnections within the brain has made significant progress in recent years. Current research has uncovered a network of intracellular signaling events that provide precise coordination of a diverse array of cellular responses, including trafficking events, cytoskeletal remodeling, gene transcription, and protein ubiquitination and translation. This chapter considers the specific cellular responses controlled by the phosphatidylinositol 3-kinase (PI3K) signaling pathway, which is instructive with regard to a number of important steps involved in the development of the brain. These range from the mediation of extrinsic signals - such as growth factors, axon guidance cues, and extracellular matrix components - to intrinsic effectors, such as downstream signaling components that act, for example, at the translation level. PI3K signaling is, consequently, at the heart of controlling neuronal migration and neuronal morphogenesis, as well as dendrite and synapse development. Many neurobehavioral disorders arise as a consequence of subtle developmental abnormalities. Unsurprisingly, therefore, aberrant PI3K signaling has been indicated by many studies to be a contributing factor to the pathophysiology of disorders such as schizophrenia and autism. In this chapter, we will focus on the specific, yet divergent, cellular processes that are achieved through PI3K signaling in neurons and are key to brain development.