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Instituto de Biomedicina y Biotecnología de Cantabria
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Regulation of gene expression during vertebrate limb development




viñetaInvestigadora principal:

Dra. Marian Ros, Profesora de Investigación CSIC

viñetaOtro personal:

  • Dra. Marian Fernández Terán, Prof. Titular Universidad
  • Dra. Federica Bertocchini, investigadora Ramón y Cajal
  • Dra. Maria del Carmen González Martín, JAE-doc
  • Dr. Carlos Garrido-Allepuz 
  • Dra. Irene Delgado Carceller, becaria postdoctoral UC
  • Patricia Sainz, becaria predoctoral JAE-pre
  • Endica Haro, estudiante predoctoral
  • Marisa Junco, técnico de laboratorio

viñetaPágina web:

viñetaTemas de investigación:

Limb development
In tetrapods, the first morphological indication of limb development is the appearance of symmetric slight swellings in the lateral body wall. After this initial budding, further limb development relies on multiple intercellular interactions directed by three signaling centers that become established in the bud as it emerges. Each center provides the signaling molecules necessary for patterning in one of the main axes of the limb. Furthermore, the function of these signaling centers is interdependent and overall emphasizes the fact that limb development is controlled by multiple cell-cell interactions. Our goal is to understand the cellular, molecular and genetic basis of these interactions. The approaches we are presently using include experimental studies with chicken embryos and the study of genetically modified mice.
Currently the group is working in the following areas of investigation:

viñetaThe role of Hox and Gli3 genes in the control of the number of digits
viñetaThe crosstalk and interactions between different signaling pathways during limb development, particularly that involving BMP signaling
viñetaThe pathways leading to the induction of the Apical ectodermal ridge
viñetaThe mechanisms controlling patterning in the proximo-distal axis and the reevaluation of the current models
viñetaThe function of Hox genes in endochondral ossification



viñetaPublicaciones relevantes (últimos 10 años)

viñetaRoselló-Díez A., Ros M.A. and Torres M. Diffusible signals, not autonomous mechanisms determine the main proximodistal limb subdivision (2011). Science (in press)
viñetaCooper 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)
viñetaGarrido-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)
viñetaTalamillo, 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
viñetaGaloway, 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.
viñetaDominguez-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.
viñetaAlvarez-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.
viñetaBastida, 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.
viñetaDelgado, I., Dominguez-Frutos, E., Schimmang, T. and Ros, M.A. (2008) The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of anterior autopod through BMP-mediated cell death. Developmental Dynamics 237: 649-658.
viñetaFernández-Terán, M.A. and Ros, M.A. (2008). The apical ectodermal ridge: Signaling pathways involved. International Journal Developmental Biology 52:857-871.
viñetaBastida, M.F. and Ros, M.A. (2008). How do we get a perfect complement of digits? Current Opinion in Genetics and Development 18:374-380.
viñetaLópez-Gracia, M.L. and Ros, M.A. (2007). Left-right asymmetry in vertebrate development.  Advances in Anatomy, Embryology and Cell Biology.  ISBN: 3-540-36347-5
viñetaSheth, R., Bastida, M.F. and Ros, M.A. (2007). Hoxd and Gli3 genes interact to control digit number. Developmental Biology 310:430-441.
viñetaFernández-Terán, M.A., Hinchliffe, J.R. and Ros, M.A. (2006).  Birth and death of cells in limb development.  A mapping study. Developmental Dynamics 235:2521-2537.
viñetaTalamillo, A., Bastida, Fernández-Terán, M.A. and Ros, M.A. (2005).  Limb development and the control of the number of digits.Clinical Genetics 67:143-153.
viñetaBastida, M.F., Delgado, M.D., Wang, B., Fallon, J.F., Fernández-Terán, M.A. and Ros, M.A. (2004) The levels of Gli3 repressor correlate with Bmp4 expression and apoptosis during limb development.Development Dynamics 231: 148-160.
viñetaRos, M.A., Dhan, R., Fernández-Terán, M.A.,  Rashka, K., Caruccio, N.C., Bitgood, J.J., Lancman, J.J. and Fallon, J.F. (2003). The chick oligozeugodactyly (ozd) mutant lacks sonic hedgehog function in the limb.  Development 130:527-537
viñetaFernández-Terán, M.A., Piedra, M.A., Rodriguez-Rey, J.C., Talamillo, A., and Ros, M.A. (2003). Pattern of expression and regulation of eHand during limb bud development. Developmental Dynamics 418:539-544
viñetaWelcher, P.T., Fernández-Terán, M., Ros, M.A., and Zeller, R. (2002). Mutual genetic antagonism involving GLI3 and dHAND prepartterns the vertebrate limb bud mesenchyme prior to SHH signalling. Genes and Development 16: 421-426
viñetaPiedra, M.E. and Ros, M.A. (2002) BMP positively regulates Nodal expression during the specification of the left-right axis in the chick embryo. Development 12: 3431- 3440
viñetaPiedra, M.E., Delgado, M.D., Ros, M.A. Leon, J. (2002) cmyc overexpression increases cell size and impairs cartilage differentiation during chick limb development. Cell Growhth and Differentiation 13: 185-193
viñetaIcardo, JM, Garcia-Rincón, J.M. Ros, M.A.  (2002) Malformaciones cardiacas, heterotaxia y lateralidad Rev. Esp. Cardiol 55:962-974
viñetaTorres, M., Couso, J.P., Ros, M.A. (2002).  Building limb buds. Embo Reports 3: 933-937
viñetaDudley, A.T., Ros, M.A., Tabin, C.E. (2002). A reexamination of proximodistal patterning during vertebrate limb development. Nature 418:539-544


Dr. Marián Ros
IBBTEC – Facultad de Medicina, Universidad de Cantabria
(+34) 942 201933