N-cadherin Acts in Concert With Slit1-Robo2 Signaling in Regulating Aggregation of Placode-Derived Cranial Sensory Neurons

Development. 2009 Dec;136(24):4155-64. doi: 10.1242/dev.034355.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cadherins / physiology*
  • Cell Adhesion / physiology
  • Chick Embryo
  • Gene Expression Regulation, Developmental
  • Nerve Tissue Proteins / metabolism*
  • Neural Crest / cytology
  • Neural Crest / physiology
  • Neurogenesis / physiology
  • Receptors, Immunologic / metabolism*
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / physiology*
  • Signal Transduction
  • Trigeminal Ganglion / cytology
  • Trigeminal Ganglion / embryology
  • Trigeminal Ganglion / physiology*

Substances

  • Cadherins
  • Nerve Tissue Proteins
  • Receptors, Immunologic