Chapter 6 - Planar Cell Polarity and the Cell Biology of Nervous System Development and Disease

Abstract

Although the role of planar cell polarity (PCP) proteins in polarized cells such as epidermal sheets is beginning to be understood, much less is known about their roles in the nervous system despite the severe neurological phenotypes observed in PCP animal mutants and human patients harboring mutations in these genes. This is complicated by the fact that “polarization” in a neuron is a relative term, since a neuron must reengage and reorient the polarity system every time the growth cone of an axon needs to change directions in response to guidance cues. This chapter will begin with a broad introduction on PCP, followed by a discussion of PCP effector genes identified in nonneuronal tissues that play roles in the nervous system. I will then provide a description of nervous system phenotypes in PCP mutants with an emphasis on neuronal migration and axonal extension defects including what is known about the cell biology of these processes. This will include a discussion on key Rho GTPases and proteins that affect microtubule and actin dynamics. In addition, I will discuss the remarkable similarities between adherens junctions (at which the classic PCP proteins reside) and focal adhesions/point contacts, the latter of which are critical for growth cone dynamics and cell migration.