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 #
5R01GM054657-15
Application #
8318585
Study Section
Special Emphasis Panel (ZRG1-BDA-L (02))
Program Officer
Hoodbhoy, Tanya
Project Start
1997-05-01
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
15
Fiscal Year
2012
Total Cost
$348,469
Indirect Cost
$123,469
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Schwieterman, Alicia A; Steves, Alyse N; Yee, Vivian et al. (2016) The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching. Genetics 202:639-60
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
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
Xu, Suhong (2015) The application of CRISPR-Cas9 genome editing in Caenorhabditis elegans. J Genet Genomics 42:413-21
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
Xu, Suhong; Chisholm, Andrew D (2014) C. elegans epidermal wounding induces a mitochondrial ROS burst that promotes wound repair. Dev Cell 31:48-60
Chuang, Marian; Chisholm, Andrew D (2014) Insights into the functions of the death associated protein kinases from C. elegans and other invertebrates. Apoptosis 19:392-7
Xu, Suhong; Chisholm, Andrew D (2014) Methods for skin wounding and assays for wound responses in C. elegans. J Vis Exp :

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