McGinnis Lab Home Page

 

Seven Hox transcript patterns in a single embryo.
microRNA-10 transcript pattern (red) in embryo
Aseptic wound response pathway in embryos
Transcription units: Dfd, Scr, and ftz in nuclei

 

  

William McGinnis
University of California, San Diego
Division of Biology
Section of Cell & Developmental Biology
9500 Gilman Drive
La Jolla, CA 92093-0349
(858) 822-0458

Bill McGinnis received his Ph.D. from UC Berkeley in 1982 and was a Jane Coffin Childs postdoctoral fellow at the University of Basel. He was a Professor at Yale University from 1984 until 1995, then moved his lab to the University of California, San Diego. He served as the Chairman of the Department of Biology from July 1998 - June 1999, as Associate Dean of the Division of Natural Sciences from July 1, 1999 - June 2000, and as Interim Dean of the Division of Biological Sciences from July 1, 2000 - February 1, 2001.

The McGinnis lab is located at the University of California, San Diego, in La Jolla, CA. The lab is on the fourth floor of Bonner Hall, on the same floor as the laboratories of James Posakony, Ethan Bier, Steve Wasserman, Raffi Aroian, Amy Pasquinelli, and Emily Troeml. Our labs have overlapping interests, shared resources, and fruitful interactions. The University and the greater La Jolla area form a community rich in world class research in life sciences and biotechnology. We are within walking distance of the Salk Institute, the Scripps Research Institute, the Burnham Research Institute and the Scripps Institution of Oceanography. Graduate students in the Division of Biological Sciences at UCSD enjoy the opportunity to rotate through and to choose labs at both the UCSD campus and the Salk Institute. Return to top of page / People / Publications

 

Research Interests:

 

1. We are studying a ancient genetic system, involving the btd/Sp8, Dll/Dlx, dac/Dach, and hth/Meis genes, that evolved to pattern the anterior head of bilateral animal embryos. We propose this patterning system was coopted multiple times to pattern the proximal distal axis of animal appendages such as the arthropod antennae and legs. (Lemons et al, 2010).

2. MicroRNA-10 (mir-10) involvement in early embryonic patterning via control of Hox gene function. MicroRNAs regulate the temporal and spatial pattern of gene function via degradation or repression of target messenger RNAs. We are exploring the function of mir-10, which is conserved in all bilateral animals and maps between the Hox protein coding genes Dfd/Hox4 and Scr/Hox5. miR-10 is expressed in a pattern reminiscent of Hox proteins in embryos (see picture above), but does not appear to be an embryonic developmental switch like the homeodomain class protein-coding genes in the Drosophila Hox gene clusters. (Lemons and McGinnis, 2006). (Lemons, Pare & McGinnis. 2012).

3. We are exploring a novel epidermal wound response pathway in Drosophila. This pathway is activated by loss of all Hox functions in a body segment, or by aseptic puncture wounds. We have aseptic wound response genes, and the cis-regulatory regions that activate reporter gene expression in cells adjacent to wounds (see picture above). The activation of some of these genes in response to breaks in the integument requires the Grainy head transcription factor. Grainy head protein homologs are conspicuously expressed in the barrier epithelium of both flies and mammals, and required for the formation and repair of an impermeable "skin" whether that skin is make of keratinocytes or cuticle. (Mace et al. 2005). We have recently identified many novel genes that regulate the transcription response to epidermal puncture wounds in Drosophila.  The functions of these genes indicate that hydrogen peroxide is one signal required for activating regeneration genes around epidermal wounds, and Flotillin-2 is inhibiting the spread of wound signals in Drosophila epidermal cells. (Juarez et al., 2011). Our study of mutants in a fungal (Neurospora) grainy head-like gene suggest that an ancestral grainy head like function was to regulate cell wall composition and remodeling, and in animals, that function was co-opted to control the formation of an apical extracellular matrix and cellular junctions that provide epithelial barrier functions. (Paré et al., 2012).

4. We have developed methods (multicolor in situ hybridization coupled with high resolution microscopy) to count mRNAs in the cytoplasm embryonic cells, at the same time as detecting transcription per se of the same gene in nuclei, in order to understand gene regulation of animal developmental pathways at the single cell level. For a recent papers on this, see Pare et al. (2009). and Arvey et al. (2010).  We are following up this research with multicolor in situ hybridization experiments to visualize enhancer-promoter interactions for Hox genes in Drosophila embryonic cells.

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