N-cadherin acts in concert with Slit1-Robo2 signaling in regulating aggregation of placode-derived cranial sensory neurons.
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.
Shiau
Celia E
CE
Division of Biology 139-74, California Institute of Technology, Pasadena, CA 91125, USA.
Bronner-Fraser
Marianne
M
D000818:Animals; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D011971:Receptors, Immunologic / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology / Q000502:physiology*
D015820:Cadherins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic