Genetic control of morfogénesis



Group leader: Ginés Morata Pérez,
Technical Assistance: Angelica Cantarero Mateo, Rosa María González Herrera,

Research Summary

In the laboratory there two research groups, led by G. Morata and E. Sanchez-Herrero respectively, focused on the genetic control of Drosophila development.

During the 2001-2002 period the research work by the Morata group has been centered in three major lines 1) Identification and study of new genetic subdivisions in the imaginal discs, 2) Study of the genes that establish the dorsal-ventral body axis in the embryo and 3) Analysis of the mechanisms controlling the size of the wing

Regarding the first issue, there are two genes encoding homeodomain transcription factors and that are expressed in restricted domains of the thorax. The muscle specific homeobox (msh) gene functions in the lateral region whereas eyegone (eyg) is active in the anterior central region. The function of the two genes is being studied by inducing mutations and misexpression experiments with the Gal4/UAS method. The results so far indicate that the two genes play critical roles in the subdivision of the thorax. For eyg it has been shown that it functions downstream the thoracic genes iroquois and pannier (pnr) and mediates their patterning function.

In the analysis of the embryonic dorsal-ventral (D/V) specification, the work focused on three genes, pnr, buttonhead (btd) and LP1, which are expressed in distinct zones along the D/V axis. In the case of pnr the evidence is that it has a selector-like function similar to that reported for the adult structures; it specifies the development of the mediodorsal region and interacts with other genes like iro and spalt responsible for the development of other dorsal regions. In contrast btd function is restricted to the Nervous System and the ventral discs primordia, antennal, leg and genital. The loss of btd function and of the related gene twin of eyegone (toe) the ventral adult structures do not form. The LP1 gene is expressed in the most dorsal zone of the embryo, the amnioserosa, and its function appears to be related with the diffusion and response to the Dpp signal, which in the embryonic development has a dorsalising function.

The analysis of the size control mechanisms is a new research topic in the group but related to experiments originated in the laboratory about 25 years ago (Morata and Ripoll, Dev. Biol. 1975). It was found that in the wing disc cells that divide slowly are eliminated if they co-exists in the same polyclone with faster dividing cells. This phenomenon was called “cell competition” and implied the existence of a cell communication process that discriminates cells with different proliferation rates. Recent work in the laboratory has shown that the elimination of slow dividing cells is due to apoptosis triggered by low levels of activity of the Dpp signalling pathway. Experiments under way try to establish a functional connection between Dpp activity, growth of the wing and apoptosis. Preliminary results indicate that the Dpp pathway promotes growth but this activity is antagonised by those of two genes, daughters against dpp (dad) and brinker (brk), which in turn are regulated by Dpp. The final size of the Drosophila wing appears to be the result of these two antagonistic forces.

The group headed by E. Sanchez-Herrero is studying the mechanisms responsible for the Hox genes specificity in the determination of the anteroposterior axis in Drosophila. The Hox gene Abdominal-B (Abd-B) is required to determine the genitalia and, in its absence, this is transformed into leg or antenna. These two appendages share with the genitalia a common positional information that is modified by Abd-B to form this structure. This is achieved by Abd-B repressing genes characteristic of legs or antennae. These two appendages are similar in many respects, however, we have identified two adjacent genes with a similar sequence that are expressed in the antenna (and the eye) but not in the leg. Ectopic expression of either of these two genes, that we have called Hernández and Fernández, makes ectopic eyes or antenna. Whether one or another structure is made depends in part on the activity of the Notch gene. We have extended previous results as to the relationship of Hox genes and signalling pathways, determined some of the mechanisms to specify fly structures and characterised two genes that mediate Hox information to make different appendages.



Publications

Morata, G. (2001) How Drosophila appendages develop. Nature Reviews Mol. Cell Biol. 2, 89-97

Morata, G. (2001) La Historia de los genes Homeóticos. Arbor 662, 229-246

Estrada, B., Sánchez-Herrero, E. (2001) The Abdominal-B Hox gene of Drosophila antagonizes appendage development. Development 128, 331-339

Morata, G. (2001) Compartmentalization. Encyclopedia of Genetics (Ed. Sydney Brenner and Jeffrey H. Miller) Academic Press, New York pp 426-427

Estrada, B., Sánchez-Herrero, E. (2001) To see or not to see. The ELSO Gazette: http://www.the-elso-gazette/magazines/issue5/ mreviews12.asp) Issue 5.

Morata, G. (2001) La revolución biológica y el futuro del hombre. En “Las incertidumbres de un mundo en mutación”. Vol. 1. pp 109-117 Forum Deusto, Universidad de Deusto Bilbao

Herranz, H., Morata, G. (2001) Different functions of pannier during Drosophila embryogenesis. Development 128, 4837-4846

Moreno, E., Basler, K., Morata, G. (2002) Cells compete for the Decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416, 755-759

Calleja, M., Renaud, O., Usui, K., Pistillo, D., Morata, G., Simpson, P. (2002) How to pattern an epithelium: lessons from achaete-scute regulation on the notum of DrosophilaGene 292, 1-12

Azpiazu, N., Morata, G. (2002) Distinct functions of homothorax in leg development in Drosophila. Mechanisms of Development 119, 55-67

Morata, G. (2002) The blueprints of animals revealed. In “Knowledge from Nature: Twenty-one discoveries that changed the world” Seminal Nature. Garwin, L. and Lincoln, T. (Eds.) pp 189-197 Japanese edition

Estrada, B., Casares, F., Busturia, A., Sánchez-Herrero, E. (2002) Genetic and molecular characterization of a novel iab-8 regulatory domain in the Abdominal-B gene of Drosophila melanogaster. Develoment 129, 5195-5204


Awards

Ginés Morata. Miembro del Comité Científico del Centro de Reuniones Internacionales de Biología de la Fundación Juan March, desde 2001.

Ginés Morata. Miembro del Comité Evaluador del Instituto de Investigaciones Bioquímicas de la Fundación Campomar. Buenos Aires (Argentina) Abril, 2001.

Ginés Morata. Premio Nacional Santiago Ramón y Cajal de Investigación en Biología 2002.

Ginés Morata. Miembro del Scientific Advisory Committee of the European Molecular Biology Laboratory (EMBO), desde 2002.


Doctoral Theses

Beatriz Estrada. “Estudio de la regulación y función del gen Hox Abdominal-B de Drosophila melanogaster”. Universidad Autónoma de Madrid. Calificación: Sobresaliente cum laude.

Hector Herranz. “Estudio de la función del gen pannier en el desarrollo embrionario de Drosophila melanogaster”. Universidad Autónoma de Madrid. Calificación: Sobresaliente cum laude.



C/Nicolás Cabrera 1 Campus de la Universidad Autónoma de Madrid.. 28049-Madrid .
Teléfono: +34-911964401 , Fax: +34-911964420 , e-mail: institucional@cbm.uam.es