Dr. Marian Ros, Full Professor (CSIC)
- Dra. Marian Fernández Terán, Associate Professor
- Dra. Rocío Pérez Gómez, postdoctoral
- Marc Fernández Guerrero, predoctoral
- Sara Lucas Toca, predoctoral
- Alejandro Castilla Ibeas, predoctoral
- Laura Galán, technician
A fundamental question in biology is how tissues and organs are built or repaired. Progress in this area is relevant not only for understanding morphogenesis in animal development, but also for potential applications in the fields of tissue engineering and regenerative medicine using stem-cell-based therapy.
During embryonic development, a major challenge is to understand the molecular basis of morphogenesis: how the formation of a particular structure is genetically and molecularly controlled. This approach needs to consider that individual cells interact with each other and that the final morphology and function of an organ ultimately result from the coordinated integration of many individual cell events.
Our group, using the developing limb as model system, has contributed to the identification of the molecular basis of the limb signaling centers and to the understanding of the function of key transcription factors such as Hand2 and Hox products. We have made important contributions towards elucidating digit patterning, how the number and identity of the digits is established and controlled during limb development. In humans, alterations in the number of digits, preferentially polydactyly, are among the most frequent congenital malformations. We have reported mutant phenotypes that support a Turing-type mechanism underlying digit patterning. We have also concentrated on the generation and characterization of murine models of human body malformations to identify the genetic and cellular defects underlying these malformations. The group has contributed more than 80 original papers, several of them in international prestigious journals including Cell, Nature, and Science.
Topics under current research in the lab include:
- the regulation of patterning and differentiation in the proximo-distal axis of the limb bud and the reevaluation of the current models
- the functional role of Sp6 and Sp8 transcription factors in limb development and the Split Hand/Foot Malformation
- the functional role of Hoxcgenes in the development and homeostasis of epidermal derivatives
- the role of Hoxand Gli3genes in the establishment of anterior-posterior asymmetries in the tetrapod limb
Spanish Government. Ministry of Science, Innovation and Universities
Relevant publications (last 10 years)
Role of Hox genes in regulating digit patterning. Pérez-Gómez R, Haro E, Fernández-Guerrero M, Bastida MF, Ros MA. Int J Dev Biol. 2018;62(11-12):797-805. doi: 10.1387/ijdb.180200mr. [PubMed]
An intrinsic cell cycle timer terminates limb bud outgrowth. Pickering J, Rich CA, Stainton H, Aceituno C, Chinnaiya K, Saiz-Lopez P, Ros MA, Towers M. Elife. 2018 Sep 3;7. pii: e37429. doi: 10.7554/eLife.37429. [PubMed]
Intrinsic properties of limb bud cells can be differentially reset. Saiz-Lopez P, Chinnaiya K, Towers M, Ros MA.
Development. 2017 Feb 1;144(3):479-486. [PubMed]
Ectoderm-mesoderm crosstalk in the embryonic limb: The role of fibroblast growth factor signaling. Mariani FV, Fernandez-Teran M, Ros MA
Dev Dyn. 2017 Apr;246(4):208-216.
CathepsinKCre mediated deletion of βcatenin results in dramatic loss of bone mass by targeting both osteoclasts and osteoblastic cells. Ruiz P, Martin-Millan M, Gonzalez-Martin MC, Almeida M, González-Macias J, Ros MA.
Sci Rep. 2016 Nov 2;6:36201.
HOX13 proteins: the molecular switcher in Hoxd bimodal regulation. Ros MA.
Genes Dev. 2016 May 15;30(10):1135-7. doi: 10.1101/gad.283598.116. [PubMed]
An intrinsic timer specifies distal structures of the vertebrate limb. Saiz-Lopez P, Chinnaiya K, Campa VM, Delgado I,
Ros MA, Towers M.
Nat Commun. 2015 Sep 18;6:8108. [PubMed]
Sp6 and Sp8 Transcription Factors Control AER Formation and Dorsal-Ventral Patterning in Limb Development. Haro E, Delgado I, Junco M, Yamada Y, Mansouri A, Oberg KC,
PLoS Genet. 2014 Aug 28;10(8):e1004468. doi: 10.1371/journal.pgen.1004468. [PubMed]
Long bone development requires a threshold of Hox function. González-Martín MC, Mallo M,
Dev Biol. 2014 Aug 15;392(2):454-65. doi: 10.1016/j.ydbio.2014.06.004.
Forward to the special issue on Hox/Tale transcription factors in development and disease. Wellik DM, Torres M,
Dev Dyn. 2014 Jan;243(1):1-3. doi: 10.1002/dvdy.24098. Epub 2013 Dec 9.
Evidence that the limb bud ectoderm is required for survival of the underlying mesoderm. Fernandez-Teran M,
Ros MA, Mariani FV.
Dev Biol. 2013 Sep 15;381(2):341-52. doi: 10.1016/j.ydbio.2013.06.032. [PubMed]
Decoupling the function of Hox and Shh in developing limb reveals multiple inputs of Hox genes on limb growth. Sheth R, Grégoire D, Dumouchel A, Scotti M, Pham JM, Nemec S, Bastida MF,
Ros MA, Kmita M.
Development. 2013 May;140(10):2130-8. doi: 10.1242/dev.089409. [PubMed]
Sheth R, Bastida MF, Kmita M, Ros M. (2014). "Self-regulation", a new facet of Hox genes' function. Dev Dyn. 2014 Jan;243(1):182-91.
Fernandez-Teran M, Ros MA, Mariani FV (2013). Evidence that the limb bud ectoderm is required for survival of the underlying mesoderm. Dev Biol. 2013 Sep 15;381(2):341-52
Sheth R, Grégoire D, Dumouchel A, Scotti M, Pham JM, Nemec S, Bastida MF, Ros MA, Kmita M. (2013). Decoupling the function of Hox and Shh in developing limb reveals multiple inputs of Hox genes on limb growth. Development. 2013 May;140(10):2130-8.
Sheth R, Marcon L, Bastida MF, Junco M, Quintana L, Dahn R, Kmita M, Sharpe J, Ros MA. (2012) Hox genes regulate digit patterning by controlling the wavelength of a Turing-type mechanism. Science. 2012 Dec 14;338(6113):1476-80.
Garrido-Allepuz C, González-Lamuño D, Ros MA. (2012) Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations. PLoS One. 2012;7(9):e44962.
- Roselló-Díez A., Ros M.A. and Torres M.
(2011). Diffusible signals, not autonomous mechanisms determine the main proximodistal limb subdivision. Science.2011; 332:1086-1088.
- Cooper K.L., Hu J K-H, Berge D., Fernandez-Teran M, Ros M.A. and Tabin C.J. (2011). Proximal-distal patterning of the vertebrate limb is initiated by altered exposure to secreted signals. Science (in press)
- Garrido-Allepuz, C., Haro, E., Gonzalez-Lamuño, D., Martinez-Frías, M.L., Bertocchini, F. and Ros M.A. (2011) Sirenomelia: A Clinical and Experimental Review. Disease Models and Mechanism (in press)
- Talamillo, A., Delgado, I., Nakamura, T., De-Vega S., Yoshitomi Y, Unda F, Birchmeier W, Hamada, Y., Ros, M.A. (2010). Role of epiprofin, azinc-finger transcription factor, in limb development. Developmental Biology 337
- Galoway, J.L., Delgado, I., Ros, M.A. and Tabin, C.J. (2009). A Reevaluation of X-Irradiation Induced Phocomelia and Proximodistal Limb Patterning. Nature 60:400-404.
- Dominguez-Frutos, E., Vendrel, V., Alvarez, Y., Zelarayan, L.C., Lopez-Herandez, I., Ros, M., Schimmang, T. (2009). Tissue-specific requirements for FGF8 during early inner ear development. Mechanisms of Development 126:873-881.
- Alvarez-Medina R., Le Dreau G., Ros M., Marti, E. (2009) Hedgehog activation is required upstream of Wnt signalling to control neural progenitor proliferation. Development 136: 3301- 3309.
- Bastida, M.F., Sheth, R. and Ros, M.A. (2009) A Bmp/Shh negative feedback loop serves to restrict Shh expresion during limb development. Development 136: 3779- 3789.