Biomedical Engineering Reference
In-Depth Information
1. OUTLINE OF REVIEW
This review summarizes the role of planar cell polarity (PCP) signaling
components in axon guidance and whether and how growth cones may use
cell polarity pathways (planar and apical-basal) or a subset of cell polarity
pathways to detect guidance cues and to turn up or down along gradients
of guidance molecules. This review also explores, for the first time, the
exciting possibility that this cell polarity signaling-based mechanism (or
module) may be a general principle in growth cone guidance.
In stark contrast to our rich knowledge of the identity of axon guidance
molecules, how signaling conveys directionality is poorly understood. The
possibility that cell polarity signaling may be a key mediator of turning will
provide answers to fundamental questions in signaling and cell biological
mechanisms of growth cone steering. The systemic and global feature of
planar polarity (also referred to as tissue polarity) and apical-basal polarity
(A-BP) suggests that this cell polarity-based signaling mechanism may be
responsible for establishing the highly organized axonal and dendritic wiring
patterns throughout the nervous system, a striking feature of neural circuitry.
Even though the growth cone is a motile structure, apparently distinct
from nonmotile epithelial sheets, there are potentially common links at
the molecular and cellular levels because the molecular and cellular compo-
nents are not “stationary” in nonmotile epithelial cells. In fact, recent work
showed that the key component in the adherence junction, E-cadherin, is
actively turned over while setting up polarity. Ongoing polarized endocy-
tosis and exocytosis in stationary epithelial cells are also widely recognized.
Insights gained from cell polarity signaling pathways in growth cones can
also shed light on general principles of cell polarity signaling. This review
focuses on PCP components, although A-BP will be included because of
the intimate interactions of these two cell polarity pathways.
2. PCP SIGNALING COMPONENTS MEDIATE AXON
GUIDANCE
Two independent studies published in 2003 converged on the surpri-
sing discovery that the Wnt family morphogens are conserved axon guidance
molecules (
Lyuksyutova et al., 2003; Yoshikawa, McKinnon, Kokel, &
Thomas, 2003
). In the vertebrate spinal cord, commissural axons that
ascend after midline crossing are attracted by Wnts, which are expressed in
an anterior-high-posterior-low (rostral high-caudal
low) graded fashion
