The Roberts lab studies the molecular controls of pattern formation in vertebrate viscera. We are currently focusing on gut and lung anterior-posterior (AP) patterning events. We use the chick embryo as a model system examining the expression of candidate factors during development of the gut and lung. Manipulation of these expression patterns yields information about their function in controlling AP pattern. We use viral mediated misexpression and electroporation to ectopically express wild type candidate factors or overexpress inhibitors/dominant negative constructs in ovo or in vitro. Analysis of the phenotypes by gross, microscopy and by molecular characterization gives insight into the normal function of the factor and its pathway/interactors.
Our studies in gut development include a focus in the factors that determine the boundaries of the AP regions of the gut: pyloric sphincter, ileocecal valve, anal sphincter. We also study pattern formation of the enteric nervous system (ENS). Our findings include a fundamental role of the Bmp pathway in ENS patterning in the chick. Other projects include dissecting the factors responsible for the rumples chicken, one of the genetic chicken lines in which caudal structures (tail, cloaca, gut) are abnormally formed, and the role of Sox9 in pyloric sphincter patterning. The factors we are studying in the gut focus of the lab include the Hox genes, Hh, Bmp, Wnt, and Sox gene families.
The Roberts lab has published primarily on gut development using the chick embryo as a model system. We are currently expanding our lung studies to include human lung development. By examining the expression of candidates during normal human fetal pulmonary development and comparing the expression with abnormal lung development we can hypothesize both on the role of the factors in human pulmonary organogenesis. We hope to find candidates in this way to identify those responsible for causing human congenital malformations of the lung. We are particularly interested incongenital cystic adenomatoid malformation and in pulmonary hypoplasia associated with diaphragmatic hernia. This translational research is a nice correlate to the experimental system using chick embryos to study lung pattern formation. The pathways we are studying include the Wnt, Hh, Bmp signaling pathways and novel factors pulled from a lung bud screen.
Representative Publications:
1. de Santa Barbara, P., and Roberts, D. J. (2002). Tail gut endoderm and gut/genitourinary/tail development: a new tissue-specific role for Hoxa13. Development 129, 551-61.
2. de Santa Barbara, P., van den Brink, G. R., and Roberts, D. J. (2002). Molecular etiology of gut malformations and diseases. Am J Med Genet 115, 221-30.
3. de Santa Barbara, P., van den Brink, G. R., and Roberts, D. J. (2003). Development and differentiation of the intestinal epithelium. Cell Mol Life Sci 60, 1322-32.
4. de Santa Barbara, P., Williams, J., Goldstein, A. M., Doyle, A. M., Nielsen, C., Winfield, S., Faure, S., and Roberts, D. J. (2005). Bone morphogenetic protein signaling pathway plays multiple roles during gastrointestinal tract development. Dev Dyn 234, 312-322.
5. Doyle, A. M., Roberts, D. J., and Goldstein, A. M. (2004). Enteric nervous system patterning in the avian hindgut. Dev Dyn 229, 708-12.
6. Goldstein, A. M., Brewer, K. C., Doyle, A. M., Nagy, N., and Roberts, D. J. (2005). BMP signaling is necessary for neural crest cell migration and ganglion formation in the enteric nervous system. Mech Dev in press.
7. Moniot, B., Biau, S., Faure, S., Nielsen, C. M., Berta, P., Roberts, D. J., and de Santa Barbara, P. (2004). SOX9 specifies the pyloric sphincter epithelium through mesenchymal-epithelial signals. Development 131, 3795-804.
8. Smith, D. M., Nielsen, C., Tabin, C. J., and Roberts, D. J. (2000). Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut boundary. Development 127, 3671-81.
9. Thayer, S. P., di Magliano, M. P., Heiser, P. W., Nielsen, C. M., Roberts, D. J., Lauwers, G. Y., Qi, Y. P., Gysin, S., Fernandez-del Castillo, C., Yajnik, V., Antoniu, B., McMahon, M., Warshaw, A. L., and Hebrok, M. (2003). Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis. Nature 425, 851-6.
10. van den Brink, G. R., Bleuming, S. A., Hardwick, J. C. H., Schepman, B. L., Offerhaus, G. J., Keller, J. J., Nielsen, C., Gaffield, W., van Deventer, S. J., Roberts, D. J., and Peppelenbosch, M. P. (2004). Indian hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. Nat Genet 36, 1-6.
Contact Information
Phone: 617-726-6460
Fax: 617-726-6656
E-mail: pbhide@partners.org
