Research Programmes
Cell & Developmental Biology
Development and Growth Control Laboratory
Marco Milán
Principal Investigator
ICREA Research Professor
Office Tel : +34 93 403 49 02
Lab Tel : +34 93 403 49 01
e-mail : marco.milan
irbbarcelona.org
Background
A central question in modern developmental biology is how the growth and patterning of tissues are controlled on a molecular and genetic level. Drosophila melanogaster provides an ideal model system to address this issue because of its suitability for genetic and molecular manipulations and its well-described developmental biology. Systematic genetic screens for loss-of-function mutations, gain-of-function phenotypes and the detection of enhancers have revealed many of the genes involved in a number of developmentally important processes. In addition, the completion of the genomic sequencing project for Drosophila makes it possible to use reverse genetic approaches, such as RNA-mediated interference, targeted gene disruption as well as genome-wide expression analyses to address a wide variety of questions concerning the developmental biology of the fruit fly.
During the development of multicellular organisms, groups of cells assemble to form tissues that are initially homogenous. The elaboration of spatial pattern often begins when the field of cells subdivides into smaller territories. The imaginal discs of Drosophila provide well-characterized experimental systems in which subdivision of the tissue depends on mechanisms that limit cell mixing to produce stable boundaries. These stable subdivisions are called compartments. In the imaginal disc compartments, boundaries serve as signalling centres. Short-range interactions between cells in adjacent compartments induce the expression of the signalling proteins Wingless (Wg) and Decapentaplegic (Dpp) in cells adjacent to the compartment boundaries. Wg and Dpp form long-range extracellular protein gradients centred on the compartment boundaries. Stable boundaries between compartments result in tightly localized sources of these signalling proteins. Intermingling of cells at the compartment boundary causes disorganization of the signalling centre with disastrous consequences for patterning and growth control.
Research Interests
The Drosophila wing imaginal disc is a monolayered epidermal sac. The wing primordium arises from the embryonic ectoderm as a group of around 30 cells that proliferate extensively during larval development to reach about 50,000 cells. The wing primordium is subdivided into an anterior (A) and a posterior (P) compartment by the restricted expression and activity of the homeodomain protein Engrailed in P cells. This subdivision is inherited from the embryonic ectoderm. When the wing primordium consists of around 100 cells, it subdivides again into a dorsal (D) and a ventral (V) compartment by the restricted expression and activity of the LIM-homeodomain protein Apterous in D cells. We aim to determine how compartment boundaries are generated, how expression of the organizing molecules Wg and Dpp is induced at the compartment boundaries and how growth and patterning is organized by the activity of Wg and Dpp at these boundaries.
Research Lines
To achieve our objectives, our group is structured around 3 research lines:
- Compartment boundary formation: identification of new genes and properties
- Signaling molecules and growth control
- Compartments and growth control
Funding
This group receives financial support from the following sources:
- European Commission
- Ministerio de Educación y Ciencia (Spanish Ministry of Science and Education)
- Generalitat de Catalunya (DURSI)(Government of Catalonia)
- ICREA (Catalan Institute of Research and Advanced Studies)
- EMBO Young Investigator Programme
