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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BDA-L (02))
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Hoodbhoy, Tanya
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University of California San Diego
Schools of Arts and Sciences
La Jolla
United States
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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
Dejima, Katsufumi; Kang, Sukryool; Mitani, Shohei et al. (2014) Syndecan defines precise spindle orientation by modulating Wnt signaling in C. elegans. Development 141:4354-65
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; Goncharov, Alexandr; Wang, Shaohe et al. (2014) The microtubule minus-end-binding protein patronin/PTRN-1 is required for axon regeneration in C. elegans. Cell Rep 9:874-83
Grossman, Emily N; Giurumescu, Claudiu A; Chisholm, Andrew D (2013) Mechanisms of ephrin receptor protein kinase-independent signaling in amphid axon guidance in Caenorhabditis elegans. Genetics 195:899-913
Xu, Suhong; Chisholm, Andrew D (2011) A G?q-Ca²? signaling pathway promotes actin-mediated epidermal wound closure in C. elegans. Curr Biol 21:1960-7
Giurumescu, Claudiu A; Chisholm, Andrew D (2011) Cell identification and cell lineage analysis. Methods Cell Biol 106:325-41
Fakhouri, Tala H I; Stevenson, Jeff; Chisholm, Andrew D et al. (2010) Dynamic chromatin organization during foregut development mediated by the organ selector gene PHA-4/FoxA. PLoS Genet 6:
Gotenstein, Jennifer R; Swale, Ryann E; Fukuda, Tetsuko et al. (2010) The C. elegans peroxidasin PXN-2 is essential for embryonic morphogenesis and inhibits adult axon regeneration. Development 137:3603-13
Kaminsky, Rachel; Denison, Carilee; Bening-Abu-Shach, Ulrike et al. (2009) SUMO regulates the assembly and function of a cytoplasmic intermediate filament protein in C. elegans. Dev Cell 17:724-35

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