Model for the Role of Jagged2a/Notch Signaling during Differentiation of Multi-Cilia Cells and Principal Cells in the Zebrafish Distal Pronephric Duct

Abstract

<p>Two adjacent cells of the developing pronephric duct are shown. The left cell, the winner in the lateral inhibition competition, differentiates as a multi-cilia cell (with cilia tuft and <i>rfx2</i> and <i>centrin2</i> expression, etc.), whereas the right cell is consequently inhibited and differentiates as a principal cell (with primary cilium and Na⁺, K⁺ ATPase expression). Activated components of the feedback regulatory system are highlighted in red, and inactive components are outlined in gray. Jagged2a is the sole ligand, Notch1a and Notch3 are two redundant receptors, and Her9 is one of the effectors that works downstream of the Notch receptors to prevent generating excessive multi-cilia cells at the expense of the principal cells. In this model, Mib affects Notch activity by interacting with Jagged2a and facilitating Jagged2a endocytosis in order to signal to neighboring cells. Procilia genes are hypothetical and have not been identified. In a manner similar to that of the proneural genes, procilia genes could encode bHLH transcription factors, stimulating expression of <i>jagged2a</i> and terminal differentiation (ciliogenesis) genes. Other components are mentioned in the text.</p