VANG-1 and PRKL-1 cooperate to negatively regulate neurite formation in Caenorhabditis elegans.
VANG-1 and PRKL-1 cooperate to negatively regulate neurite formation in Caenorhabditis elegans.
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DOI：
10.1371/journal.pgen.1002257
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发表时间：
2011-09
期刊：
影响因子：
4.5
通讯作者：
Colavita A
中科院分区：
文献类型：
--
作者：
Sanchez-Alvarez L;Visanuvimol J;McEwan A;Su A;Imai JH;Colavita A
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. Neurons are among the most morphologically complex cells in the body. Early in development, newly born neurons project one or more processes called neurites that will eventually mature into axons and dendrites. While the genetic determinants that promote neurite emergence along specific trajectories are beginning to be elucidated, the cellular and molecular pathways that prevent inappropriate neurite formation to maintain proper neuronal morphology and prevent superfluous connections are largely unknown. Van Gogh and Prickle dependent-PCP signaling is a well-established regulator of cellular polarity especially along the surface of epithelial cells. In this study, we show that a conserved 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. In particular, we show that loss of PRKL-1 results in neurons with too many neurites while PRKL-1 overexpression results in too few neurites. Our findings suggest that mechanisms that specifically block inappropriate neurite formation may be required to ensure proper neuronal connectivity in higher organisms.
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DOI：
10.1523/jneurosci.4508-10.2010
发表时间：
2010-11-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fenstermaker AG;Prasad AA;Bechara A;Adolfs Y;Tissir F;Goffinet A;Zou Y;Pasterkamp RJ
通讯作者：
Pasterkamp RJ
影响因子：
5.3
作者：
Kishida, S;Yamamoto, H;Kikuchi, A
通讯作者：
Kikuchi, A
影响因子：
25
作者：
Adler, CE;Fetter, RD;Bargmann, CI
通讯作者：
Bargmann, CI
影响因子：
56.9
作者：
Colavita, A;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M
影响因子：
2.7
作者：
Gupta, BP;Sternberg, PW
通讯作者：
Sternberg, PW