PgmNr W4054: BAR-1 and CCAR-1 cooperate to properly position a subset of motor neurons along the AP axis.

Authors:
Jeffrey Hung 1,2 ; Matt Tanner 1,2 ; Antonio Colavita 2


Institutes
1) University of Ottawa, Ottawa, Ontario, Canada; 2) OHRI, Ottawa, Ontario, Canada.


Keyword: Cell polarization

Abstract:

There are three classes of embryonically derived motor neurons (DD, DA and DB) that are organized into a very stereotypical pattern along the ventral nerve cord (VNC). For example, the six DD neurons (DD1-6) are evenly spaced along the AP axis and each are invariably situated between the same DA or DB neighbour. The planar cell polarity pathway (PCP) is a non-canonical Wnt pathway involved in establishing cell and tissue polarity. Recently we discovered that disruption of a PCP like pathway that includes highly conserved genes such as vang-1/Van Gogh and prkl-1/Prickle result in DD, DA and DB spacing defects. Imaging of comma to 1.5 fold stage embryos revealed that these defects are caused by delays in the cell intercalations that ultimately generates the linear profile of motor neurons along the ventral nerve cord. To identify new genes involved in motor neuron positioning or tiling we examined other conserved components of canonical and non-canonical Wnt pathways for DD position defects.  We found that mutations in bar-1/beta-catenin displayed a highly penetrant phenotype in which DD1 and DD2 are clustered together at all larval stages instead of being properly spaced/tiled in the VNC.  We found the same phenotype, although somewhat milder, in ccar-1/cell division cycle and apoptosis regulator-like-1 mutants.  CCAR1 is a transcriptional regulator that in vertebrates has been shown to physically interact with beta-catenin to control the expression of Wnt regulated genes. In bar-1 and ccar-1 mutants DD2 is displaced anteriorly closer to DD1. PRY-1/Axin is a negative regulator of the Wnt signalling pathway as a part of a destruction complex involved in degrading BAR-1/β-catenin. Interestingly, pry-1 mutants also have a DD1-DD2 spacing defect but one in which DD1 is displaced posteriorly closer to DD2.  In all three mutants, the spacing of the other DD neurons (DD3-6) are not strongly affected. These findings suggest that a non-canonical Wnt pathway may be involved in properly separating DD1 and DD2 during VNC formation or elongation of the embryo..