Morphogenesis of epithelial tissues such as the skin involves complex interplay of autonomously generated forces, cell-cell interactions, and the extracellular matrix. The C. elegans epidermis is a model epithelium whose development can be dissected with single cell resolution. Our studies address three aspects of epidermal development. First, in embryonic epidermal enclosure the epidermal epithelium spreads over substrate neurons. Using semi- automated cell tracking we that the neuronal substrate is highly dynamic during enclosure. We will address how these collective neuronal migrations are driven and their relationship to epidermal spreading movements.
Our second aim addresses the function of a family of secreted enzymes, the peroxidasins, in epidermal development and wound healing. Epithelial spreading movements and wound healing processes may share related mechanisms. We have developed a model for epidermal wound healing in C. elegans. We will characterize the role of calcium signaling in wound repair in the epidermis. We will use genetics to analyze a mutant that appears to undergo spontaneous epidermal wounding. These three aims will explore interrelated aspects of epidermal morphogenesis and repair. A better understanding of these processes will shed light on functions of conserved signaling pathways in development and will improve our knowledge of the molecular basis of wound repair.

Public Health Relevance

The proposed work is aimed at understanding the genetic basis of tissue morphogenesis, focusing on how cells interact during the development of the skin and nervous system. Increased understanding of this process has implications for human birth defects such as neural tube closure. Understanding similarities between epithelial morphogenesis and wound healing will elucidate how epidermal cells sense and respond to damage.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054657-17
Application #
8633463
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hoodbhoy, Tanya
Project Start
1997-05-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
17
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Xu, Suhong; Wang, Zhiping; Kim, Kyung Won et al. (2016) Targeted Mutagenesis of Duplicated Genes in Caenorhabditis elegans Using CRISPR-Cas9. J Genet Genomics 43:103-6
Chuang, Marian; Hsiao, Tiffany I; Tong, Amy et al. (2016) DAPK interacts with Patronin and the microtubule cytoskeleton in epidermal development and wound repair. Elife 5:
Xu, Suhong; Chisholm, Andrew D (2016) Highly efficient optogenetic cell ablation in C. elegans using membrane-targeted miniSOG. Sci Rep 6:21271
Chisholm, Andrew D; Hutter, Harald; Jin, Yishi et al. (2016) The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans. Genetics 204:849-882
Xu, Suhong (2015) The application of CRISPR-Cas9 genome editing in Caenorhabditis elegans. J Genet Genomics 42:413-21
Kang, Sukryool; Lee, Chen-Yu; Gonçalves, Monira et al. (2015) Tracking epithelial cell junctions in C. elegans embryogenesis with active contours guided by SIFT flow. IEEE Trans Biomed Eng 62:1020-33
Loer, Curtis M; Calvo, Ana C; Watschinger, Katrin et al. (2015) Cuticle integrity and biogenic amine synthesis in Caenorhabditis elegans require the cofactor tetrahydrobiopterin (BH4). Genetics 200:237-53

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