CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOA

Gene expression control, patterning and growth during appendage development

Research summary:

The formation of an adult organism from a single fertilized egg is a highly regulated and complex process. It involves the generation of large number of cells with specialized functions that need to be assembled together in tissues and organs. This process, named morphogenesis, requires the specification within developmental fields of territories with the ability to acquire different fates and coordinated cell behaviors. Territorial specification depends on the precise modification of gene expression in both time and space and it is mediated by a specific set of transcription factors encoded by selector and selector-like genes. Selector proteins regulate the formation and identity of tissues and organs activating a special developmental program that is implemented in collective cell behaviors. Cell proliferation, apoptosis or cell shape changes are some of the cellular processes that control the shape and final form an organ.  

Functional maintenance of tissues and organs depends on the elimination of defective cells. Misspecified cells or with damage in their DNA are often eliminated by apoptosis. Therefore, a correct balance between cell fate specification, cell proliferation and apoptosis is essential to maintain tissue homeostasis. Defects in the control and coordination of any of these processes are the hallmark of tumor progression.

Our main general aim is to decipher the molecular mechanisms that control cell fate specification and tissue homeostasis during development. To this end we use the development of Drosophila appendages as our model.

We have two objectives in the lab:

1) Specification, patterning and morphogenesis of appendages: We study how legs and wings are specified in the embryo and how they are later subdivided in territories with different cell fates to generate the characteristic adult pattern. We also investigate how these specific gene expression programs are implemented in terms of collective cell behaviors. At the molecular level, a small number of signaling pathways and transcription factors are reiteratively used throughout development to specify and pattern the appendages in Drosophila and in vertebrates.

2) Coordination between cell proliferation and apoptosis during tissue homeostasis: The tumor suppressor p53 is a key player in the coordination of cellular responses after multiple stresses such as DNA damage. These responses include the cell cycle arrest, the activation of DNA repair mechanisms and, if the damage is too severe, apoptosis. Defects in the ability to trigger and coordinate any of these responses are a major cause of cancer development. In this work, we use Drosophila to study the connection between cell cycle progression and the apoptotic response after DNA damage.

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Figure 1: Time course of the specification of the wing and leg primordia in a Drosophila embryo. A group of cells from the leg primordia  (green) give rise to part of the wing (blue). Red marks cell membranes.

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Figure 2: The image is a composition of a wild-type leg imaginal disc showing the folds that prefigure the tarsal joints (upper side) and a dysf mutant leg where the folds are absent (lower side). Dlg (yellow), Nuclear marker (Blue) and F-Actin (Red-White).

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Figure 3: Leg phenotypes obtained after a progressive reduction in the dose of Sp family genes in Drosophila.

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* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Cristobal VargasSara4402Estudiante TFG
Estella SagradoCarlos415.34402cestella(at)cbm.csic.esE.Científicos Titulares de Organismos Públicos de Investigación
Pereira FernándezJavier4214402Estudiante TFG
Rodríguez RuízAlonso4214436alonso.r(at)cbm.csic.esGJ-AI_Tit. Sup. Actividades Técn. y Prof.GP1
Ruiz LosadaMireya4214436mireya.ruiz(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1 66%
Tur GraciaSara4214402sara.tur(at)cbm.csic.esTit.Sup.Activ.Técn.y Profes. GP1 66%

Relevant publications:

Collaborators:

Richard Mann (Columbia University, NYC)

Markus Affolter (Biozentrum, Basel)

Matthew Slattery (Univ. of Minnesota, MN)

Jose Felix de Celis (CBMSO)

Antonio Baonza (CBMSO)

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