| Cell migration is a dramatic and critical behavior that contributes to normal embryonic development and to pathologies such as inflammatory disease and tumor metastasis. The vast majority of studies of cell migration have historically focused on cells migrating in vitro; however cells look and behave differently in vivo. To study cell migration in vivo, we have developed a simple and genetically tractable model system, which is the migration of a small group of cells during ovarian development in the fruitfly, Drosophila melanogaster. The vast array of sophisticated genetic tools have allowed studies of this organism have solved fundamental problems in biology, such as the molecular basis of pattern formation during embryonic development. Using genetic screens, we have identified dozens of genes that are required for the communication between migrating border cells and all the other cells in their microenvironment. We have discovered that multiple signals, which emanate from all different cell types in their surroundings, control various aspects of the border cells' movement. For example, growth factors produced in the oocyte, the cell that is the target of the migration, act as chemoattractants instructing the cells where to go. A cytokine secreted from a special pair of cells determines which 4-8 cells, out of 650, will acquire the ability to migrate and invade. A steroid hormone coordinates the timing of this migration with the progression of oogenesis in general, which is dependent on the nutritional status of the organism. Highly related molecular signals also contribute to tumor metastasis in humans. Recently we have developed organ culture conditions that support border cell migration and egg chamber development ex vivo, allowing us to make time-lapse movies of the migrating cells. Studying the cellular and molecular dynamics of this process in normal and mutant egg chambers will be a major focus for the future.
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Silver, D.
L., Naora H., Liu,
J., Cheng, W.
and Montell, D. J.
(2004) Activated STAT3: localization
in focal adhesions and function
in ovarian cancercell motility. Cancer
Research15:3550-8.
PubMed Reference
Yoshida, H.,
Cheng, W.,
Hung, J.,
Montell,
D., Geisbrecht, E., Rosen,
D., Liu, J. Naora,
H. (2004)
Lessons from border cell
migration
in the Drosophila ovary:A
role for
myosin
VI in migration
of human
ovarian cancer
, PNAS, 101:8144-8149. Geisbrecht, E.
R. and Montell,
D. J. (2004) A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. Cell,
118;111-25.
PubMed Reference
Pinheiro, E. M.
and Montell,
D. J. (2004)
Requirement
for Par-6 and Bazooka
in Drosophila Border
Cell Migration. Development,
131:5243-51.
Adam, JC and Montell,
DJ. (2004)
A role for extra macrochaetae downstream
of Notch
in follicle
cell differentiation. Development, 131(23):5971-5980.
PubMed Reference
Silver, D., Geisbrecht,
E. and Montell,
D. J. (2005)
Requirement for JAK/STAT signaling throughout border cell migration in Drosophila. Development,
132:3483-92.
PubMed Reference
Wang, X.,
Bo, J.,
Bridges,
T.,
Dugan, K.D.,
Chi, T.-C.,
Chodosh,
L.A.
and Montell,
D. J.
(2006) Analysis
of cell migration
using whole
genome expression
profiling
of cells
in the Drosophila ovary, Developmental
Cell, 10:483-95.
PubMed Reference
Mc.Donald, J.A.,
Pinheiro, E.,
Kadlec, L.,
Schupbach,
G. and Montell,
D. J. (2006)
Multiple EGFR ligands
participate in guiding
migrating border cells. Developmental
Biology 296:94-103.
PubMed Reference
Wang, X., Adam, J.C. and Montell,
D. J. (2007)
Spatially localized Kuzbanian required for specific activation of Notch during border cell migration., Developmental
Biology,
301(2):532-40.
PubMed Reference Prasad, M. and Montell, D.J. (2007) Cellular and molecular mechanisms of border cell migration analyzed using time-lapse live-cell imaging. Developmental
Cell, 12(6):997-1005.
PubMed Reference
Prasad, M., Jang, A.C., Starz-Gaiano, M., Melani, M., and Montell D.J. (2007) A protocol for culturing Drosophila melanogaster stage 9 egg chambers for live imaging.
Nature Protocols2(10):2467-73.
PubMed Reference
Melani, M., Simpson, K.J., Brugge, J.S., and Montell D.J. (2008) Regulation of cell adhesion and collective cell migration by hindsight and its human homolog RREB1.
Current Biology.18(7):532-7.
PubMed Reference
Starz-Gaiano, M., Melani, M., Wang, X., Meinhardt, H., and Montell D.J. (2008) Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population.
Developmental
Cell, 14(5):726-38.
PubMed Reference
McDonald, J.A., Khodyakova, A., Aranjuez, G., Dudley C., Montell, D.J. (2008) PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells. Current BiologyNov 11;18(21):1659-67.
PubMed Reference
Jang, A. C.-C., Chang, Y.-C., Bai, J. and Montell, D.J. Spatial and temporal control of border cell migration requires integration of cytokine and steroid hormone signals mediated by the BTB protein Abrupt. Nature Cell Biology, in press.
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