Segmental specification and pattern formation in Drosophila
One important question in developmental biology is to understand the mechanisms that control size, shape and pattern of different structures in each organism. Our aim is to study these issues in Drosophila melanogaster, with a special focus in the analysis of Hox genes. These genes specify the identity of different structures along the anteroposterior axis of all the bilaterians. The Hox genes code for proteins that bind DNA and regulate the expression of downstream genes, which eventually determine changes in form, size and pattern in different organs.
Size and shape control by Hox genes
We study how the Hox genes determine the different size of particular organs. We investigate, for instance, how the Hox gene Ultrabithorax controls the different size of the adult metanotum (dorsal part of the third thoracic segment, T3), and that is greatly reduced as compared to the mesonotum (dorsal part of the second thoracic segment, T2). In Ultrabithorax mutants the T3 is transformed into T2, so this gene reduces the size of the T3. In a similar analysis, we would like to know the mechanisms whereby Hox genes regulate different proliferation in the histoblasts, cells that give rise to the abdomen, or in the imaginal discs, since the former divide only during pupal stages and the latter mainly during the larval period. Finally, we want to analyze the reason for the size difference in the segments that form the genitalia, which requires the coordination between the Hox gene Abdominal-B and the sex determination genes. The different proliferation of the genital disc segments is established by the Hox Abdominal-B gene together with sex determination genes and is mediated, among others, by the Decapentaplegic and Hippo signaling pathways (Fig. 1).
We also study how Hox genes determine form. Thus, we analyze the mechanisms whereby Ultrabithorax determines the globular form of the halteres (dorsal appendages in the thorax) as opposed to the flat appearance of wings. We think this difference may be implemented by changes in the extracellular matrix in early pupal stages regulated by Ultrabithorax.
Figure 1. Expression scheme of Metalloproteinase 1 (Mmp1) and collagen (encoded by the viking gene, vkg) in the wing and haltere imaginal discs. In the latter Ubx prevents the apposition of dorsal and ventral epithelia and the flat shape of the wings.
The elimination of an abdominal segment
Drosophila males lack a seventh abdominal segment (A7) whereas females have it (albeit reduced). Although histoblasts are present in the A7 during the larval period, they are extruded in pupal stages, as the larval cells are, and for this process it is required the activity of the Abdominal-B Hox gene and of sex-determination pathway. We want to study how these genes regulate the elimination of this segment at a certain time in pupal development (video 1). We are also interested in the possible functional connection between elimination of this segment and rotation of the male genital plate, that occurs in pupa (video 2).
Given the essential role of Abdominal-B in the development of the posterior abdomen and genitalia, we will explore the functional role of the different conserved motifs of the Abdominal-B protein in the formation of these structures. In particular, we will study the function of Abdominal-B proteins mutated in these motifs in the extrusion of male A7 cells and the requirement of the Extradenticle and Homothorax cofactors for this process.
Video 1. Video showing the removal of the abdominal histoblasts of the male A7 (small cells in the upper lateral side) and the larval cells (large, centrally located). The A6 histoblasts abut the genitalia , which is in the inal steps of its 360° rotation (top).The cells are marked with neuroglian-GFP.
Video 2. The genital plate rotates 360º in pupa. The cells are marked with nrg-GFP (in green) and posterior cells with Hh-Dsred (in red).
Regeneration and Hox genes
Drosophila imaginal discs have been used as a model for studying processes of cell reprogramming. After damaging or removing parts of an imaginal disc there is recovery thereof mediated by different signals. It has been shown that during the regeneration of imaginal discs transgressions of compartments take place, with possible changes in cell identity, including those determined by Hox genes. To analyze this point, we are to study the changes of expression of homeotic genes that occur during regeneration of the genital disc, an imaginal disc formed by the fusion of three segments with distinct homeotic information (Fig. 2).
Figure 2. Male genital disc in which death was induced in the caudal domain and regenerated afterwards. The expression of Caudal (red) is more limited than that of ß-galactosidase (green) marking the caudal lineage. Topro is in blue.
|Last name||Name||Laboratory||Ext.*||Professional category|
|Cazalla Ibañez||Eduardo||424||4700||Estudiante TFM|
|Lombardo Hernandez||Juan||424||4699||Estudiante TFG|
|Martín Fernández||María Paloma||424||4700||mpmartin(at)cbm.csic.es||E. Técnicos Superiores Especializados de Organismos Públicos de Investigación|
|Sánchez-Herrero Arbide||Ernesto||424||4699||esherrero(at)cbm.csic.es||E. Profesores de Investigación de Organismos Públicos de Investigación|
|Yagüe Serrano||Roberto||424||4699||GJ-AI_Tit. Sup. Actividades Técn. y Prof.GP1|
- de Navas, L. F., Garaulet, D. L. y Sánchez-Herrero, E. (2006). The Ultrabithorax Hox gene of Drosophila controls haltere size by regulating de Dpp pathway. Development 133, 4495-4506. http://dev.biologists.org/content/133/22/4495.full.pdf+htm
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Manjón, C., Sánchez-Herrero, E. y Suzanne, M. (2007). Sharp boundaries of Dpp signaling trigger local cell death required for Drosophila leg morphogenesis. Nat.Cell Biol 9, 57-63. http://www.nature.com/ncb/journal/v9/n1/pdf/ncb1518.pdf
Comentado en Milán, M. Nat.Cell Biol 9, 17-18 (2007) http://www.nature.com/ncb/journal/v9/n1/pdf/ncb0107-17.pdf y en J. Cell Biol. 176, 4 (2007) http://jcb.rupress.org/content/176/1/4.full.pdf+html
- Garaulet, D. L., Foronda, D., Calleja, M. y Sánchez-Herrero, E. (2008). Polycomb-dependent Ultrabithorax Hox gene silencing induced by high Ultrabithorax levels in Drosophila. Development 135, 3219-3228. http://dev.biologists.org/content/135/19/3219.full.pdf+html
de Navas, L. F., Reed, H., Akam, M., Barrio, R., Alonso, C.R. y Sánchez-Herrero, E. (2011). Integration of RNA processing and expression level control modulates the function of the Drosophila Hox gene Ultrabithorax during adult development. Development 138, 107-116. http://dev.biologists.org/content/138/1/107.full.pdf+html
Foronda, D., Martín, P., y Sánchez-Herrero, E. (2012) Drosophila Hox and sex-determination genes control segment elimination through EGFR and extramacrochetae activity. PLoS Genet. e1002874. doi: 10.1371/journal.pgen.1002874. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415437/pdf/pgen.1002874.pdf
Curt J. R., de Navas, L. F. y Sánchez-Herrero, E. (2013). Differential activity of Drosophila Hox genes induces myosin expression and can maintain compartment boundaries. PLoS ONE e571. doi: 10.1371/journal.pone.0057159. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581558/pdf/pone.0057159.pdf
Sánchez-Herrero, E. (2013). Hox targets and cellular functions. Scientifica 738257. doi: 10.1155/2013/73825. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892749/pdf/SCIENTIFICA2013-738257.pdf
- Guarner, A., Manjón, C., Edwards, K., Steller, H., Suzanne, M. y Sánchez-Herrero, E. (2014). The zinc finger homeodomain-2 gene of Drosophila controls Notch targets and regulates apoptosis in the tarsal segments. Dev. Biol. 385, 350-365.
- Garaulet, D.L., Castellanos, M.C., Bejarano, F., Sanfilippo, P., Tyler, D.M., Allan, D.W., Sánchez-Herrero, E.* y Lai, E.C*. (2014). Homeotic function of Drosophila Bithorax-Complex miRNAs mediates fertility by restricting multiple Hox genes and TALE cofactors in the central nervous system. Dev. Cell 23, 635-648. doi: 10.1016/j.devcel.2014.04.023. http://www.ncbi.nlm.nih.gov/pubmed/24909902.
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- de Navas, L., Foronda, D., Del Saz, D. ¡ Sánchez-Herrero, E. (2014). A genetic strategy to obtain P-Gal4 elements in the Drosophila Hox genes. Methods Mol. Biol. 1196, 49-57. doi: 10.1007/978-1-4939-1242-1_4. http://link.springer.com/protocol/10.1007%2F978-1-4939-1242-1_4.
- Foronda, D., Curt, J.R., Prieto, N., Martín, P. y Sánchez-Herrero, E. (2015). The elimination of an adult segment by the Hox gene Abdominal-B. Mech. Dev. 138, 210-217. doi: 10.1007/978-1-4939-1242-1_4. http://www.sciencedirect.com/science/article/pii/S0925477315300186
- De Las Heras, J. M., García-Cortés, C., Foronda, D., Pastor-Pareja, J. C., Shashidhara, L. S., y Sánchez-Herrero E. (2018). The Drosophila Hox gene Ultrabithorax controls appendage shape by regulating extracellular matrix dynamics. Development 1
- Recomendado en F1000 https://f1000.com/prime/733362447
- Recomendado en F1000 https://f1000.com/prime/733362447
- Romero-Pozuelo, J., Foronda, D., Martín, P., Hudry, B., Merabet, S., Graba, Y. and Sánchez-Herrero E. (2019). Cooperation of axial and sex specific information controls Drosophila female genitalia growth by regulating the Decapentaplegic pathway. Dev. Biol. 454, 145-155. https://www.ncbi.nlm.nih.gov/pubmed/31251896