Protocadherin-19 and N-cadherin interact to control cell movements during anterior neurulation

The protocadherins comprise the largest subgroup within the cadherin superfamily, yet their cellular and developmental functions are not well understood. In this study, we demonstrate that pcdh19 (protocadherin 1 9) acts synergistically with n-cadherin (ncad) during anterior neurulation in zebrafish. In addition, Pcdh19 and Ncad interact directly, forming a protein-protein complex both in vitro and in vivo. Although both molecules are required for calcium-dependent adhesion in a zebrafish cell line, the extracellular domain of Pcdh19 does not exhibit adhesive activity, suggesting that the involvement of Pcdh19 in cell adhesion is indirect. Quantitative analysis of in vivo two-photon time-lapse image sequences reveals that loss of either pcdh19 or ncad impairs cell movements during neurulation, disrupting both the directedness of cell movements and the coherence of movements among neighboring cells. Our results suggest that Pcdh19 and Ncad function together to regulate cell adhesion and to mediate morphogenetic movements during brain development.