Cell and Developmental BiologyDevelopment and Growth Control Laboratory

Development and Growth Control Laboratory
Group Leader

ICREA Research Professor

+34 93 40 34902

During the development of multicellular organisms, body growth is controlled at the scale of the organism by the activity of long-range signaling molecules, mostly hormones. These systemic factors coordinate growth between developing tissues and act as relays to adjust body growth in response to environmental changes. In target organs, long-range signals act in concert with tissue-autonomous ones to regulate the final size of a given tissue.

 

The interplay between systemic and tissue-autonomous signals contributes to define the final size of a tissue or organ. Drosophila imaginal discs, simple epithelial invaginations that grow one thousand fold in mass and cell number, are probably one of the best model systems to analyze at the genetic and molecular level the control of size in a growing epithelium. My lab uses the wing imaginal disc to dissect the cellular and molecular mechanisms underlying the regulation of tissue growth.

 

We take an integrative approach as we aim to understand how the final size of the developing wing is achieved not only during normal development but also in stress conditions. In this regard, we are dissecting the cellular and molecular mechanisms underlying the homeostatic capacity of the tissue to several insults (with a special interest in genomic instability) and its potential impact in tumorigenesis. This integrative approach helps to understand the robust interplay between systemic and tissue-autonomous signals in normal development or in stress situations, and contributes to identify emerging stress signalling molecules transiently induced to compensate for tissue loss that can contribute to tumorigenesis in a condition of chronic expression.

 

  1. Morphogens and tissue growth: Morphogens are signalling molecules expressed in restricted domains that spread to the rest of the tissue to form a concentration gradient. A complex set of interactions between morphogens and their corresponding signalling pathways contributes to organizing limb growth along the dorsal-ventral, anterior-posterior and proximal-distal axes. We are currently analyzing how these morphogens and their gradients regulate wing growth.

  2. Systemic hormones and tissue growth: Wing primordia are embedded in the open circulatory system of the feeding larva and the activity of the major nutrient sensing pathways modulates the final size of the developing wing according to nutrient availability. We are currently analyzing the interplay between nutrient sensing pathways and tissue-autonomous signals, including morphogens and their gradients, in regulating wing growth.

  3. Chromosomal instability and tissue homeostasis. Chromosomal instability (CIN) often results in aneuploidy, which compromises cell fitness and leads to cell death. Despite the dramatic levels of apoptosis observed in wing primordia subject to CIN, the impact on the size of the resulting adult wing is mild. We are currently dissecting the molecular mechanisms used at the cellular and tissue-wide level to dampen the deleterious effects of CIN in the wing epithelium.
  4. Chromosomal instability and tumorigenesis. Wing primordia subjected to CIN produce tumor-like overgrowths, metastatic behavior and malignancy to the host upon blockade of the apoptotic machinery, and this tumorigenic response relies mainly on the production of highly aneuploid cells that delaminate from the epithelium and activate a JNK-dependent transcriptional response. We are currently dissecting the cellular and molecular mechanisms underlying CIN-induced tumor growth, metastatic behavior and malignancy.
Recasens-Alvarez C, Ferreira A and Milán M.
Nat Commun, 8 13815 (2017)
Clemente-Ruiz M, Murillo-Maldonado JM, Benhra N, Barrio L, Pérez L, Quiroga G, Nebreda AR and Milán M.
Dev Cell, 36 (3), 290-302 (2016)
Boulan L, Martín D and Milán M.
Curr Biol, 23 (6), 473-8 (2013)
Dekanty A, Barrio L, Muzzopappa M, Auer H, and Milán M
P Natl Acad Sci Usa, 109 (50), 20549-54 (2012)
Duran J, Tevy MF, Garcia-Rocha M, Calbó J, Milán M* and Guinovart JJ*.
EMBO Mol Med, 4 (8), 719-29 (2012)
Mesquita D, Dekanty A and Milán M.
Plos Biol, 8 (12), e1000566 (2010)
Becam I, Fiuza UM, Arias AM and Milán M.
Curr Biol, 20 (6), 554-60 (2010)
Herranz H, Hong X, Pérez L, Ferreira A, Olivieri D, Cohen SM and Milán M.
Embo J, 29 (10), 1688-98 (2010)
Herranz H, Pérez L, Martín FA and Milán M.
Embo J, 27 (11), 1633-45 (2008)

* shared senior authorship

This group receives financial support from the following sources:

  • 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
  • Ministerio de Economía y Competitividad (MINECO)
  • European Commission (EC), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa"

     

Group news & mentions

13 Jan 2017

"Gaceta Médica” devotes an article to the study headed by ICREA Professor Marco Milán.

<p>Ectopic wings upon ectopic activation of JAK/STAT (Carles Recasens-Alvarez and Ana Ferreira, IRB Barcelona)</p>
9 Jan 2017

Many of the secrets of life, such as how we become a certain size and shape, have been uncovered in studies performed over more than 100 years and involving animal models such as the fruit fly

9 Jan 2017

Various media report on the study headed by ICREA Professor Marco Milán, leader of the Development and Growth Control Lab at IRB Barcelona.

Upcoming events

23 Feb
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Toni Celià-Terrassa, PhD. Department of Molecular Biology, Princenton University, NJ (USA)
24 Feb
Sala Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Dr. Fanni Gergely, Cancer Research UK Cambridge Institute, University of Cambridge, UK
27 Feb
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Prof. Dr. Donghan Lee, BioNMR Group. Brown Cancer Center University of Louisville. Department of Medicine, University of Louisville, USA