The goal of this application is to determine the cellular and molecular mechanisms that underlie the formation and function of ciliated epithelia, using the larval skin of Xenopus as a model system. The Xenopus larval skin is directly analogous to the pulmonary epithelium of mammals but is extremely accessible to experimental analysis using molecular approaches and imaging. Using this model, the proposed experiments will determine how ciliated cells are specified by transcription factors, and how their insertion into the epithelium is regulated by the Notch signaling pathway. The proposed experiments will also determine the molecular pathways that are required to establish the polarity of ciliated cells within the plane of the epithelium. Finally, the proposed experiments will establish assays to study cilia function. Relevance: Many organ systems are lined with an epithelia that interacts with an aqueous environment. To function properly, this epithelia contains specialized ciliated cells whose beating action sets up a directed fluid flow. Such ciliated epithelia play important physiological functions in the respiratory tract, the central nervous system and in reproductive organs, and when defective cause a class of human disease called primary ciliary dysfunction (PCD). For example, ciliated cell dysfunction in the pulmonary epithelium leads to recurrent respiratory infections, a common problem in children, while other forms of cilia dysfunction cause hydrocephaly, situs inversus, and infertility. Despite the importance of ciliated epithelia to organ function and to human health, very little is known about how such tissues form during embryonic development. Results from these studies will provide important basic information about how ciliated cell dysfunction may arise in human disease, and provide strategies for treating the loss of ciliated cells using cell replacement.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM076507-02
Application #
7124291
Study Section
Development - 1 Study Section (DEV)
Program Officer
Haynes, Susan R
Project Start
2005-09-21
Project End
2009-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$370,679
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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