Research Grants

Award Year 2007

SAWAMOTO Kazunobu
NONAKA Shigenori
SPASSKY Nathalie
Fluid flow in developmental biology

Fluid-flow-based mechanisms are involved in several developmental processes in vertebrates. In the node, the twirling of primary cilia creates a leftward flow (called "nodal flow") that is essential for the left-right axis formation of embryos. In the adult mammalian brain, the coordinated beating of ependymal cilia is responsible for cerebrospinal fluid (CSF) flow (called "ependymal flow") that is crucial for neuroblast migration from their germinal zone toward the olfactory bulb. Interestingly, we and others have observed that both node and neural progenitor cells display a primary cilium on their apical surface. For this project, we thus hypothesize that in both systems, primary cilia are crucial sensors of fluid flow as well as of its contents and that this sensory function contributes to both developmental processes. To test this hypothesis, we will combine novel and innovative hydrodynamic and biological in vivo and in vitro approaches. The main questions to be answered are 1) what are the mechanisms of nodal and CSF flow dynamics, 2) how ependymal and nodal cilia become polarized and motile during development, 3) how nodal and neural primary cilia sense fluid flow and its contents, and 4) what are the integrated consequences of defective fluid flow in neuronal migration and morphogenesis? Collaborative work by our team, which includes experts in hydrodynamics, embryology and neurobiology, is anticipated to unveil novel concepts and create a research field providing important information on basic problems in biology.