A major unsolved problem in developmental biology is how organisms break symmetry along the left-right body axis. In the mouse, this process involves generation of a leftward fluid flow across the embryonic node. This nodal flow is created, and possibly sensed, by cilia on the node cells. How do the cilia know which way to drive the fluid? Theoretical computations as well as the investigators' preliminary experimental fluid-dynamics studies indicate that cilia could drive a leftward flow if they were tilted to the posterior. Preliminary scanning electron microscopy analysis confirms that such a posterior tilt exists for node cilia. However, how is this tilting aligned relative to the anterior-posterior axis? The direction a cilium points is dictated entirely by the centriole that produces the cilium. The investigators propose to determine the basis of posterior ciliary tilt by examining the orientation of the centrioles which produce the node cilia. They will ask what aspect of centriole orientation is altered in response to anterior-posterior axis cues. As part of this analysis, the investigators will test whether node centrioles are rotationally oriented relative to the midline, as predicted for a mechanosensory model for flow sensing. Taken together, the proposed experiments will test the hypothesis that the centriole is the key structure that links the left-right axis to the anterior-posterior and dorsal-ventral axes. If the investigators find that centrioles are indeed oriented relative to the body axes during left-right determination, this would provide the foundation for future experiments to determine the cell polarity pathways and cytoskeletal elements that produce this defined orientation. ? ? ?
| Feldman, Jessica L; Marshall, Wallace F (2009) ASQ2 encodes a TBCC-like protein required for mother-daughter centriole linkage and mitotic spindle orientation. Curr Biol 19:1238-43 |
| Marshall, Wallace F; Kintner, Christopher (2008) Cilia orientation and the fluid mechanics of development. Curr Opin Cell Biol 20:48-52 |
| Feldman, Jessica L; Geimer, Stefan; Marshall, Wallace F (2007) The mother centriole plays an instructive role in defining cell geometry. PLoS Biol 5:e149 |
