ABSTRACT
Most vertebrate embryos establish left-right (LR) asymmetry by a cilia-driven, unidirectional leftward flow of extracellular components. Leftward flow thus represents the initial mechanism for symmetry breakage. To underscore its importance, the ciliated tissue executing this task is termed left-right organizer (LRO). In order to determine laterality, flow directionality has to be sensed and transformed into intracellular signaling. Therefore, the LRO is partitioned into central flow-generating (cLRO) and flanking flow-sensing cells (sLRO), which project motile or non-motile cilia, respectively. How sensing occurs remains unclear, but we do know the molecular target of flow-induced signaling. In sLRO cells, the interaction between the Tgfß morphogen Nodal and its Cerberus-like inhibitor Dand5 is regulated in a flow-dependent manner. Flow represses Dand5 expression on the left side, and subsequently Nodal is able to fix the left positional information by inducing left asymmetric gene expression. Intriguingly, our recent data suggest that flow triggers a post-transcriptional response which interferes with dand5 mRNA translation and promotes its decay. This chapter focuses on the Nodal/Dand5 module and how post-transcriptional regulation contribute to symmetry breakage. In addition, we argue that the Xenopus system offers exceptional experimental advantages in analyzing processes downstream of flow sensing, which could be used to understand the functional consequences of human mutations leading to laterality defects.
