Abstract
Neuritogenesis is a critical early step in the development and maturation of neurons and neuronal circuits. While extracellular directional cues are known to specify the site and orientation of nascent neurite formation in vivo, little is known about the genetic pathways that block inappropriate neurite emergence in order to maintain proper neuronal polarity. Here we report that the Caenorhabditis elegans orthologues of Van Gogh (vang-1), Prickle (prkl-1), and Dishevelled (dsh-1), core components of planar cell polarity (PCP) signaling, are required in a subset of peripheral motor neurons to restrict neurite emergence to a specific organ axis. In loss-of-function mutants, neurons display supernumerary neurites that extend inappropriately along the orthogonal anteroposterior (A/P) body axis. We show that autonomous and non-autonomous gene activities are required early and persistently to inhibit the formation or consolidation of growth cone protrusions directed away from organ precursor cells. Furthermore, prkl-1 overexpression is sufficient to suppress neurite formation and reorient neuronal polarity in a vang-1– and dsh-1–dependent manner. Our findings suggest a novel role for a PCP–like pathway in maintaining polarized neuronal morphology by inhibiting neuronal responses to extrinsic or intrinsic cues that would otherwise promote extraneous neurite formation.
Highlights
Post-mitotic neurons undergo a transition from a more or less symmetrical morphology to a highly polarized one with axonal and dendritic projections that are precisely oriented along body or tissue axes [1,2]
We show that a conserved planar cell polarity (PCP)–like pathway consisting of VANG-1/Van Gogh, PRKL-1/Prickle, and DSH-1/Dishevelled is involved in maintaining the polarized morphology of a subset of neurons in the nematode C. elegans
Our findings suggest that mechanisms that block inappropriate neurite formation may be required to ensure proper neuronal connectivity in higher organisms
Summary
Post-mitotic neurons undergo a transition from a more or less symmetrical morphology to a highly polarized one with axonal and dendritic projections that are precisely oriented along body or tissue axes [1,2]. Neurite emergence is the first overt sign of polarization in newly born neurons followed by differentiation of these neurites into axons and dendrites. Asymmetrically distributed directional cues such as Netrins and Slits have been shown to polarize protrusive activity in neuronal somas to specify the site of nascent neurite emergence in vivo [3,4]. In addition to mechanisms that promote neurite formation, the establishment and maintenance of a polarized morphology require mechanisms that suppress non-specific neurite growth at all other times. The inhibitory pathways that act in vivo to prevent extraneous neurite formation are poorly understood
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