The multiple roles of Notch signaling during left-right patterning.

The establishment of left-right (LR) asymmetry is regulated by intricate signaling mechanisms during embryogenesis and this asymmetry is critical for morphogenesis as well as the positioning of internal organs within the organism. Recent progress including elucidation of ion transporters, leftward nodal flow, and regulation of asymmetric gene expression contributes to our understanding of how the breaking of the symmetry is initiated and how this laterality information is subsequently transmitted to the organ primordium. A number of developmental signaling pathways have been implicated in this complex process. In this review, we will focus on the roles of the Notch signaling pathway during development of LR asymmetry. The Notch signaling pathway is a short-range communication system between neighboring cells. While Notch signaling plays essential roles in regulating the morphogenesis of the node and left-specific expression of Nodal in the lateral plate mesoderm, a hallmark gene in LR patterning, Notch signaling also suppresses the expression of Pitx2 that is a direct downstream target of Nodal during later stages of development. This negative activity of Notch signaling towards left-specific activity was recently shown to be inhibited by the B cell lymphoma 6 (BCL6)/BCL6 co-repressor (BcoR) transcriptional repressor complex in a target-specific manner. The complex regulation of Notch-dependent gene expression for LR asymmetry will be highlighted in this review.