Tissue morphogenesis and cell invasions in Drosophila oogenesis
Increased cell proliferation and disrupted cellular architecture in epithelial tissues is responsible for generating the
majority of metastatic tumors in mankind. Our understanding of the pathogenesis of cancer would thus benefit greatly by increasing
our knowledge of how signaling and adhesion networks contribute to the genesis and maintenance of epithelial tissues. We are
approaching this problem in vivo using Drosophila egg chambers to ask questions using a variety of genetic, cell biology, and
molecular approaches. Egg chambers offer an excellent system for cell biological analysis because they have a relatively simple
architecture, comprised of large germ cells surrounded by a monolayer follicular epithelium. Further, the coordinated maturation
of germ cells with the follicular epithelium provides an excellent system to study the synchronous development of two distinct
tissue types. We have conducted a detailed analysis of some of the signaling and adhesion pathways that coordinate morphogenesis
of these tissues, which has given us insight into phylogenetically conserved cellular programs crucial for the development and
maintenance of epithelial tissues.
Our efforts are currently focused on understanding the function of the Drosophila tumor suppressor Discs large. Analysis of
Discs large provides a novel model to analyze cell invasions in Drosophila, and is also significant because the human Discs large
protein directly associates with APC, the most commonly mutated tumor suppressor in colon cancer cells. Discs large is localized
at the cortical cytoskeleton and consists of an SH3 motif essential for interaction with components of the actin cytoskeleton as
well as three PDZ motifs essential for interaction with membrane spanning molecules, and thus provides a link between the cell
surface and cytoskeleton. Genetic analysis has demonstrated that the Discs large PDZ motifs are essential for blocking cell
invasion, and we have identified two candidate transmembrane cell adhesion molecule that binds to this motif. We are identifying
additional molecules that directly interact with Discs large, and are exploring how these molecules interplay with Discs large to
maintain a tissue barrier during development. These studies will deepen our knowledge about the cellular and molecular mechanisms
associated with epithelial pathologies such as metastatic tumors.
Selected Publications
Goode S, Wright D, Mahowald AP (1992) The neurogenic locus brainiac cooperates with the Drosophila
EGF receptor to establish the ovarian follicle and to determine its dorsal-ventral polarity. Development 116:177-192.
Goode S, Morgan M, Liang Y-P, Mahowald AP (1996) brainiac encodes a novel secreted protein that cooperates
with Grk TGFα to produce the follicular epithelium. Developmental Biology 178:35-50.
Goode S, Melnick M, Chou T-B, Perrimon N (1996) The neurogenic genes egghead and brainiac define a
novel signaling pathway essential for epithelial morphogenesis during Drosophila oogenesis. Development
122:3863-3879.
Goode S, Perrimon N (1997) Inhibition of patterned cell shape change and cell invasion by Discs large during
Drosophila oogenesis. Genes and Development 11:2532-2544.
Goode S, Perrimon N (1997) Brainiac and Fringe are similar pioneer proteins that impart specificity to Notch
signaling during Drosophila development. Cold Spring Harbor Symposia on Quantitative Biology
62:177-184.
Goode S (2000) Germ cell cytonemes? Trends in Cell Biology 10:89-90.
Huang J, Rajkovic A, Szafranski P, Ochsner S, Orsulic S, Richards S, Goode S (2002) Expression of Drosophila
neoplastic tumor suppressor genes discs large, scribble, and lethal giant larvae in the mammalian ovary.
Gene Expression Patterns 3:3-11.
Contact Information
- Scott A. Goode, Ph.D.
- Department of Pathology
- Baylor College of Medicine
- One Baylor Plaza S201
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-8828
- Fax: (713) 798-1228
- E-mail: sgoode@bcm.tmc.edu
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