A long-term goal of our lab is to understand the molecular basis of cell polarity and tissue morphogenesis in vertebrate embryos. Our focus here is on the Planar Cell Polarity (PCP) signaling cascade, a molecular mechanism that governs both the formation of cilia and cell movements called convergent extension. Cilia are microtubule-based projections of the cell with important roles in a wide range of human pathologies. For example, the directed fluid flow generated by ciliated cells is crucial for the function of the nervous system, the kidney, the reproductive systems, and the airway. Such """"""""ciliopathies"""""""" include cystic kidney diseases, obesity syndromes, infertility, situs abnormalities, and morphological defects on the central nervous system. Convergent extension cell movements are required for neural tube closure in vertebrates, including humans. This proposal will examine the role of the PCP protein, Fritz, in ciliogenesis and convergent extension. During ciliogenesis, we will ask what role Fritz plays in polyglutamylation of microtubules and in the organization of the septin cytoskeleton. During convergent extension, we will ask how Fritz controls cell behaviors, including membrane protrusive activity and centrosomal positioning. Together, these experiments will help us to understand how PCP signaling influences such diverse cellular processes as convergent extension and ciliogenesis.
A long-term goal of our lab is to understand the molecular basis of cell polarity and tissue morphogenesis in vertebrate embryos. Our focus here is on molecular mechanisms that governs the formation of cilia and cell movements called convergent extension. The work proposed here is significant because it should further our understanding of common human birth defects, such as spina bifida. The work will also shed new light on the molecular underpinnings of a growing class of pathologies associated with defective ciliogenesis, the so-called ciliopathies.
| Adler, Paul N; Wallingford, John B (2017) From Planar Cell Polarity to Ciliogenesis and Back: The Curious Tale of the PPE and CPLANE proteins. Trends Cell Biol 27:379-390 |
| Toriyama, Michinori; Lee, Chanjae; Taylor, S Paige et al. (2016) The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery. Nat Genet 48:648-56 |
| Session, Adam M; Uno, Yoshinobu; Kwon, Taejoon et al. (2016) Genome evolution in the allotetraploid frog Xenopus laevis. Nature 538:336-343 |
| Wallingford, John B (2010) Planar cell polarity signaling, cilia and polarized ciliary beating. Curr Opin Cell Biol 22:597-604 |
