Marian Ros (IP)

  • IBBTEC. Albert Einstein 22, PCTCAN, 39011 Santander
  • marian.ros@unican.es
  • +34 682883376
  • Regulation of Gene Expression During Development
  • Principal Investigator
  • Developmental Biology
  • Department of Cell & Molecular Signalling

Marian Ros is Full Professor and Chair of the Department of Molecular & Cellular Signaling at the IBBTEC. Prof. Ros completed her MD degree with honors at the University of Cantabria in 1982 and received her PhD degree from the same university in 1986. After a postdoctoral stay at the laboratory of John Fallon (University of Wisconsin-Madison, USA) studying the roles of Msx and Hox genes in limb development, she established her own research group devoted to understand the molecular basis of morphogenesis: how the formation of a particular form or structure is genetically and molecularly controlled during vertebrate development. Using the limb as a paradigm, Prof. Ros lab has provided relevant information on the molecules and mechanisms contributing to shape an organ, always with a translational interest towards disease, repair and regeneration. Prof. Ros has always combined research with education teaching Human Anatomy and Embryology, Neuroanatomy and Developmental Biology to undergraduate and graduate students. Prof. Ros is member of the Royal Academy of Medicine of Cantabria and the awardee of the 2013 Prize of Investigation Consejo Social de la Universidad de Cantabria.

​Regulation of Gene Expression during Development


Research lines 

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 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.

Using the developing limb as model system, our group has contributed to the molecular characterization 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, and reported mutant phenotypes that support a Turing-type mechanism underlying digit patterning. Through mouse genetics, and more recently using functional genomic technologies, we have generated and characterized murine models of human congenital malformations to identify the underlying genetic and cellular defects. In particular, the implementation in the lab of CRISPR/Cas9 genome editing in mice through the electroporation of zygotes has permitted the analysis of the functional contribution of genomic regions in an efficient, rapid and high-throughput manner.

The group has contributed more than 90 original papers, several of them in international prestigious journals including Cell, Nature, and Science. 

Topics under current research in the lab include: 

  • the functional role of Hoxc genes in the development and homeostasis of epidermal derivatives (nail and hair)
  • the role of Lmx1b regulation in dorso-ventral limb patterning and its implication in morphogenesis, evolution and disease (the Nail Patella syndrome).
  • the regeneration of the digit tip and the influence of dorso-ventral polarity
  • the role of Hox and Gli3 genes in the establishment of anterior-posterior asymmetries in the tetrapod limb, and especially in the formation of the thumb.
  • the functional role of Sp6 and Sp8 transcription factors in limb development and the Split Hand/Foot Malformation
  • Hox/ERK interactions in development and cancer
  • the regulation of patterning and differentiation in the proximo-distal axis of the limb bud and the reevaluation of the current models



Funding

Spanish Government. Ministry of Science and Innovation
Mammalian-specific ectodermal enhancers control the expression of Hoxc genes in developing nails and hair follicles

Mammalian-specific ectodermal enhancers control the expression of Hoxc genes in developing nails and hair follicles

Marc Fernandez-Guerrero, Nayuta Yakushiji-Kaminatsui, Lucille Lopez-Delisle, Sofía Zdral, Fabrice Darbellay, Rocío Perez-Gomez, Christopher Chase Bolt, Manuel A. Sanchez-Martin, Denis Duboule, Maria A. Ros

Proc Natl Acad Sci U S A. 2020 Nov 16;202011078. doi: 10.1073/pnas.2011078117. Online ahead of print. 


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Identification of limb-specific Lmx1b auto-regulatory modules with Nail-Patella Syndrome pathogenicity

Endika Haro, Florence Petit, Charmaine U. Pira, Conor D. Spady, Lauren A. Ivey, Austin L. Gray, Fabienne Escande, Anne-Sophie Jourdain, Andy Nguyen, Florence Fellmann, Jean-Marc Good, Christine Francannet, S.Manouvrier-Hanu, Marian A. Ros, Kerby C. Oberg

[bioRxiv]

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Sonic hedgehog specifies flight feather positional information in avian wings.

Sonic hedgehog specifies flight feather positional information in avian wings.

Lara Busby, Cristina Aceituno, Caitlin McQueen, Constance A Rich, Maria A Ros, Matthew Towers

​Development. 2020;147(9):dev188821.

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Sp8 regulatory function in the limb bud ectoderm

Rocío Pérez-Gómez, Marc Fernández-Guerrero, Víctor Campa, Juan F. Lopez-Gimenez, Alvaro Rada-Iglesias, Maria A. Ros

[bioRxiv]

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The formation of the thumb requires direct modulation of Gli3 transcription by Hoxa13

The formation of the thumb requires direct modulation of Gli3 transcription by Hoxa13

Maria Félix Bastida, Rocío Pérez-Gómez, Anna Trofka, Jianjian Zhu, Alvaro Rada-Iglesias, Rushikesh Sheth, H. Scott Stadler, Susan Mackem and Marian Ros

​Proc Natl Acad Sci U S A. 2020 Jan 14;117(2):1090-1096.

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Role of Hox genes in regulating digit patterning.

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.

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An intrinsic cell cycle timer terminates limb bud outgrowth.

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.

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Ectoderm-mesoderm crosstalk in the embryonic limb: The role of fibroblast growth factor signaling.

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.

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Intrinsic properties of limb bud cells can be differentially reset

Intrinsic properties of limb bud cells can be differentially reset

Patricia Saiz-Lopez, Kavitha Chinnaiya, Matthew Towers, Maria A. Ros

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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.

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CathepsinKCre mediated deletion of βcatenin results in dramatic loss of bone mass by targeting both osteoclasts and osteoblastic cells.

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.

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HOX13 proteins: the molecular switcher in Hoxd bimodal regulation.

Ros, MA

​Genes Dev. 2016 May 15;30(10):1135-7.

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An intrinsic timer specifies distal structures of the vertebrate limb.

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.

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Sp6 and Sp8 transcription factors control AER formation and dorsal-ventral patterning in limb development.

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, Ros MA

​PLoS Genet. 2014 Aug 28;10(8):e1004468.

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Long bone development requires a threshold of Hox function.

González-Martín MC, Mallo M, Ros MA.

​Dev Biol. 2014 Aug 15;392(2):454-65.

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"Self-regulation", a new facet of Hox genes' function

"Self-regulation", a new facet of Hox genes' function

Rushikesh Sheth, Maria Félix Bastida, Marie Kmita, Marian Ros

​Dev Dyn. 2014 Jan;243(1):182-91.


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Forward to the special issue on Hox/Tale transcription factors in development and disease.

Wellik DM, Torres M, Ros MA.

​Dev Dyn. 2014 Jan;243(1):1-3.

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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

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Evidence that the limb bud ectoderm is required for survival of the underlying mesoderm.

Sheth R, Bastida MF, Kmita M, Ros M.

​Dev Dyn. 2014 Jan;243(1):182-91.

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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.

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Hox genes regulate digit patterning by controlling the wavelength of a Turing-type mechanism.

Sheth R, Marcon L, Bastida MF, Junco M, Quintana L, Dahn R, Kmita M, Sharpe J, Ros MA.

​Science. 2012 Dec 14;338(6113):1476-80.

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Sirenomelia phenotype in bmp7;shh compound mutants: a novel experimental model for studies of caudal body malformations.

Garrido-Allepuz C, González-Lamuño D, Ros MA.

​PLoS One. 2012;7(9):e44962.

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Initiation of proximal-distal patterning in the vertebrate limb by signals and growth.

Cooper, K.L., Hu, J. K-H, ten Berge, D., Fernandez-Teran, M., Ros M.A. and Tabin, C.J.

​Science. 2011; 332:1083-1086.

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Diffusible signals, not autonomous mechanisms, determine the main proximodistal limb subdivision.

Roselló, A., Ros M.A. and Torres, M.

​Science. 2011; 332:1086-1088.

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A clinical and experimental overview of sirenomelia: insight into the mechanisms of congenital limb malformations

Garrido-Allepuz, C, Haro, E, Gonzalez-Lamuño, D, Martinez-Frías, ML, Bertocchini, F and Ros MA.

​Disease Models and Mechanisms. 2011; 4:289-299.

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Role of Epiprofin, a zinc-finger transcription factor, in limb development

Talamillo A, Delgado I, Nakamura T, de-Vega S, Yoshitomi Y, Unda F, Birchmeier W, Yamada Y, Ros M.

​Developmental Biology. 2010; 337:363.

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A BMP-Shh negative-feedback loop restricts Shh expression during limb development

Bastida, M.F., Sheth, R. and M.Ros, M.A.

​Development. 2009; 136:3779- 3789.

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Hedgehog activation is required upstream of Wnt signalling to control neural progenitor proliferation

Alvarez-Medina R, Le Dreau G, Ros M, Martí E.

​Development. 2009 Oct;136(19):3301-9.

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Tissue-specific requirements for FGF8 during early inner ear development

Domínguez-Frutos E, Vendrell V, Alvarez Y, Zelarayan LC, López-Hernández I, Ros M, Schimmang T.

​Mech Dev. 2009 Jul 18.

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A Reevaluation of X-Irradiation-induced Phocomelia and Proximodistal Limb Patterning

Galloway JL, Delgado I, Ros MA, Tabin CJ.

​Nature. 2009 Jul 16;460(7253):400-4

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Alejandro Castilla Ibeas

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Laura Galán

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Sara Lucas Toca

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Sofía Zdral Noguero

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