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| General
Interests |
|
The
overall goal of our lab is
to understand the molecular mechanisms that link cell growth, cell
division, and cell fate patterning during development. Animal growth
results from the precise coordination of these different processes, as
well as from complex interactions between neighboring cells within
individual organs and tissues. Although the molecular pathways
that control cell proliferation, cellular biosynthesis, and cell fate
specification are known, what remains unclear is how they intersect and
are influenced by each other during the development of tissues and
organs. To this end we are carrying out studies in vivo to determine
the mechanisms that link growth to pattern formation, using the Drosophila wing as a
model system.
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| The role of Wingless in growth regulation of the developing wing |
Wingless
(Wg), a member of the conserved Wnt gene family of pattern regulators,
is a major organizer of cell fates in the developing wing and is also
believed to control wing growth. Through the use of genetics and
molecular biology, we aim to identify the growth regulatory
targets and mechanisms used by Wingless to control cellular growth,
cell cycle progression, and cell survival in vivo. The Drosophila wing imaginal disc. Wingless staining is shown in red, nuclear staining in green. The disc is oriented as described in the upper right hand corner: A, anterior; P, posterior; D, dorsal; V, ventral. Image taken from Johnston, L.A. and Sanders, A.L. 2003. Wingless promotes cell survival but constrains growth during Drosophila wing development. Nature Cell Biology, 5 (9): 827-833 (Abstract, PDF).  The zone of non-proliferating cells (ZNC) at the dorsal/ventral boundary of the wing disc and the genes involved in its setup and maintenance. Johnston, L. A. and Edgar, B. A. 1998. Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing. Nature 394, 82-84. (Abstract, PDF) |
| Intrinsic control of organ size |
|
What
is the genetic program intrinsic to organs that regulates their size?
Our observations suggest that organs such as the wing "sense" anomalous
growth rates and compensate by altering overall growth. We are
using a series of genetic and molecular assays to understand how this
occurs. Our experiments address how developing organs like wings
monitor their mass, how cells sense growth rate differences between
themselves, which growth parameters (cell cycle, cellular growth, cell
survival) respond to growth alterations, and determine how these
features interact to control wing size and shape. We are carrying out
experiments that will identify the direct cell cycle, cell survival,
and cellular growth targets regulated in situations of aberrant growth,
as well as the critical intercellular signals and signal transduction
targets important for overall organ size regulation.
 The size difference between two
male Drosophila: one
wildtype, one
carrying a mutation in Drosophila
myc (dmyc).
Image taken from Johnston, L. A., Prober, D. A., Edgar, B. A., Eisenman, R. N., and Gallant, P. 1999. Drosophila myc regulates cellular growth during development. Cell 98, 779-790. (Abstract, PDF) |
| Genetic approach to study cell competition |
Cell
competition occurs when slow-growing cells reside within a population
of faster growing ones, with the result that the cells with a growth
disadvantage are targeted for death. To study this phenomenon, we are
using a genetic approach to generate three types of cell clones with
differing growth rates within the same organ, to uncover and follow the
mechanisms used by the organ to deal with cell competition. A clonal assay of cell competition that utilizes three clone types. Mitotic recombination produces a GFP-expressing "Gal4" clone (green) and its "Sibling", marked by a cell surface marker (red). An independant recombination event produces a B-galactosidase-marked "Neutral" clone (blue). de la Cova, C., Abril, M., Bellosta, P., Gallant, P., and Johnston, L. A. Drosophila Myc regulates organ size by inducing cell competition. Cell, 117: 107-116. (Abstract, PDF) |