N-cadherin acts in concert with Slit1-Robo2 signaling in regulating aggregation of placode-derived cranial sensory neurons
- Creators
- Shiau, Celia E.
- Bronner-Fraser, Marianne
Abstract
Vertebrate cranial sensory ganglia have a dual origin from the neural crest and ectodermal placodes. In the largest of these, the trigeminal ganglion, Slit1-Robo2 signaling is essential for proper ganglion assembly. Here, we demonstrate a crucial role for the cell adhesion molecule N-cadherin and its interaction with Slit1-Robo2 during gangliogenesis in vivo. A common feature of chick trigeminal and epibranchial ganglia is the expression of N-cadherin and Robo2 on placodal neurons and Slit1 on neural crest cells. Interestingly, N-cadherin localizes to intercellular adherens junctions between placodal neurons during ganglion assembly. Depletion of N-cadherin causes loss of proper ganglion coalescence, similar to that observed after loss of Robo2, suggesting that the two pathways might intersect. Consistent with this possibility, blocking or augmenting Slit-Robo signaling modulates N-cadherin protein expression on the placodal cell surface concomitant with alteration in placodal adhesion. Lack of an apparent change in total N-cadherin mRNA or protein levels suggests post-translational regulation. Co-expression of N-cadherin with dominant-negative Robo abrogates the Robo2 loss-of-function phenotype of dispersed ganglia, whereas loss of N-cadherin reverses the aberrant aggregation induced by increased Slit-Robo expression. Our study suggests a novel mechanism whereby N-cadherin acts in concert with Slit-Robo signaling in mediating the placodal cell adhesion required for proper gangliogenesis.
Additional Information
© 2009 Company of Biologists Ltd. Accepted October 12, 2009; first published online November 23, 2009. We thank Drs J. Raper and Z. Kaprielian for the CMV-Robo2FL-myc plasmid; Dr M. Takeichi for the pCMV-cN/FLAG-pA plasmid; members of M.B.-F. laboratory for discussions and technical support; and Dr M. Barembaum for critical comments on the manuscript. This work was supported by US National Institutes of Health (NIH) National Research Service Award 5T32 GM07616 to C.E.S. and NIH grant DE16459 to M.B.-F. Deposited in PMC for release after 12 months.Attached Files
Published - Shiau2009p6516Development.pdf
Supplemental Material - 034355-FigS1.jpg
Supplemental Material - 034355-FigS2.jpg
Supplemental Material - 034355-FigS3.jpg
Supplemental Material - 034355-FigS4.jpg
Supplemental Material - 034355-FigS5.jpg
Files
Name | Size | Download all |
---|---|---|
md5:f2e4d700f87fe883a792368c1af98ec2
|
278.3 kB | Preview Download |
md5:add5e919c44bb46f2724de014366590b
|
85.4 kB | Preview Download |
md5:5e2af3e86cc1d24677b47c674fdc4dc4
|
10.9 kB | Preview Download |
md5:39d0009e39fa8db0bcdc72b7723bd5ad
|
394.3 kB | Preview Download |
md5:52570639368668e4edc6799c09b70cad
|
232.7 kB | Preview Download |
md5:a213b5c4208ca7884328d017481c126a
|
128.8 kB | Preview Download |
md5:91957f96f9c919b9ba393e1206b39af6
|
787.0 kB | Preview Download |
md5:be7e33beabc40e8bc506eb3c4fa90ced
|
4.2 MB | Preview Download |
Additional details
- PMCID
- PMC2781051
- Eprint ID
- 16918
- Resolver ID
- CaltechAUTHORS:20091209-093920989
- 5T32 GM07616
- NIH
- DE16459
- NIH
- Created
-
2009-12-09Created from EPrint's datestamp field
- Updated
-
2021-11-08Created from EPrint's last_modified field