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Juan Carlos I. Belmonte

Juan Carlos I. Belmonte

Professor
Gene Expression Laboratory

"Our ultimate goal is to try to understand the molecular and cellular basis of organ and tissue regeneration."

Ever since the first adult cells were converted into induced pluripotent stem cells (iPSCs), they have generated excitement as an alternative to embryonic stem cells and a potential source for patient-specific stem cells. Unfortunately, reprogramming adult cells into iPSCs is a slow, inefficient, and costly process and carries the risk of cancer, limiting the cells' therapeutic value. Two recent studies in Izpisúa Belmonte's lab, however, offer the prospect of safer, faster, and more efficient approaches to coaxing cells back in time.

The most widely used technology involves the forced expression of four transcription factors in fully committed adult cells: Oct4, Sox2, Klf4, and c-Myc. Because only a tiny fraction of cells transmogrify into iPSCs that look and act like embryonic stem cells, Izpisúa Belmonte wondered whether the process used to reprogram the cells was inducing a response that stopped them from growing. Izpisúa Belmonte and his team showed that adding Klf4 and c-Myc, which are oncogenes, activated the pathway for the tumor suppressor p53. In cells genetically engineered to lack p53, reprogramming efficiency increased at least tenfold, clearly demonstrating the important role that p53 played in reining in cells trying to revert back into a stem-like state. Because iPSCs generated with the full complement of reprogramming factors can turn malignant, Izpisúa Belmonte and his team also tried reprogramming mouse cells lacking p53 using only Oct4 and Sox2. The cells readily converted into iPSCs and gave rise to healthy, full-term mice that were able to reproduce, passing the ultimate test for pluripotent embryonic stem cells.

In related work, Izpisúa Belmonte's group set out to transform immunologically immature hematopoietic stem cells isolated from umbilical cord blood into iPSCs. They not only successfully converted them using only Oct4 and Sox2, but did so in less time than any previously published methodology. The resulting iPSCs were indistinguishable from human embryonic stem cells and passed all standard tests for pluripotency, establishing the possibility of a comprehensive bank of tissuematched, cord blood-derived stem cells.

Lab Photo

Left to right:
Back row: Athanasia Panopoulos, Emmanuel Nivet, Jun Li, Leo Kurian, Sergio Menendez, Sunny Yang

Front row: Ilir Dubova, Basam Barkho, Guanghui Liu, Chris Walsh, Alex Bukrinsky, Concepcion Rodriguez Esteban, Juan Carlos Izpisúa Belmonte, May Schwarz, Scott Stewart

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Juan Carlos I. Belmonte

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Home > Faculty & Research > Faculty > Juan Carlos Izpisúa Belmonte

Faculty

Juan Carlos Izpisúa Belmonte

Professor
Gene Expression Laboratory

Juan Carlos Izpisúa Belmonte, a professor in the Gene Expression Laboratory, studies how genes and molecules orchestrate the development of an embryo. The questions addressed by the laboratory include: How does one cell give rise to millions of cells, and how do they come to be organized into complete structures such as limbs, a heart or brain? How stems cells differentiate and give rise to over 200 cell types that constitute the human body? How certain animals are able to regenerate their tissues and organs, i.e., what are the genetic pathways responsible for epimorphic regeneration, a complex biological process by which animals can regenerate tissues and even entire organs throughout their lifetime after injury or amputation?

The Izpisúa Belmonte laboratory utilizes different in vivo (mouse, chick, frog, and axolotl) and in vitro (human and mouse stem cells) model systems, as well as in silico modeling approaches, with particular emphasis on the genetic pathways involved in heart and bone development and regeneration. Their research has helped to discover some of the molecules that instruct embryonic stem cells to give rise to specific cell types during embryo development, and how these cells interact with one another to form tissues and organs with proper morphology and function. This ensures that our body's organs develop and function correctly and, at the same time, are placed in their correct positions.

In addition to improving our knowledge on early human development, the research activities of Dr. Izpisúa Belmonte's laboratory are relevant to understanding the causes that underlie human birth defects, as well as to the future development of regenerative medicine.

Education

Bachelor's of Pharmacy and Science, University of Valencia
Ph.D., Universities of Bologna, Italy and Valencia, Spain
Postdoctoral fellow, University of Marburg; The European Molecular Biology Laboratories at Heidelberg, Germany; University of California, Los Angeles

Selected Publications

Aasen, T. and Izpisúa Belmonte, J.C. (2009) Isolation and cultivation of human keratinocytes from skin or plucked hair for the generation of induced pluripotent stem cells. Nature Protocols. In Press.
Ibanes, M. and Izpisúa Belmonte, J.C. (2009) Left-right asymmetry determination. Wiley Interdisciplinary Reviews: Systems Biology and Medicine. In Press.
Aran B, Rodriguez-Pizà I, Raya A, Consiglio A, Muñoz Y, Barri PN, Izpisúa JC, Veiga A (2009) Derivation of human embryonic stem cells at the Center for Regenerative Medicine in Barcelona In Vitro Cellular & Developmental Biology - Animal. In press
B.Aran, A.Veiga, J.C. Izpisúa (2009) Células madre pluripotentes Revista Arbor. In press.
Tramullas, M., Diaz, A., San-Emeterio, E.P., Morchon, N., Lantero, A., Merino, D., Buscher, D., Merino, R., Hurle, J.M., Izpisúa Belmonte, J.C. and Hurle, M. (2009) BMP and Activin membrane-bound inhibitor (BAMBI) reveal the involvement of the TGF-b family in pain modulation. Journal of Neuroscience. In Press.
Mizrak, S.C., Chikhovskaya, J.V., Sadri-Ardekani, H., van Daalen, S., Korver, C.M., Hovingh, S.E., Roepers-Gajadien, H.L., Raya, A., Fluiter, K., de Reijke, Th.M., de la Rosette, J.J.M.C.H., Izpisúa Belmonte, J.C., van der Veen, F., de Rooij, D.G. and van Pelt, A.M.M. (2009) Embryonic Stem Cell-like Cells Derived from Adult Human Testis. Human Reproduction. In Press.
Stewart, S., Tsun, Z.Y. and Izpisúa Belmonte, J.C. (2009) A histone demethylase is necessary for regeneration in zebrafish. PNAS. Published Online Nov. 6, 2009.
Rodriguez-Piza, I., Richaud-Patin, Y., Vassena, R., Gonzalez, F., Barrero, M.J., Veiga, A., Raya, A. and Izpisúa Belmonte, J.C. (2009) Reprogramming of human fibroblasts to induced pluripotent stem cells under xeno-free conditions. Stem Cells. Published Online Nov. 3, 2009.
Giorgetti, A., Montserrat, N., Aasen, T., Rodriguez-Piza, I., Vassena, R., Gonzalez, F., Boue, S., Barrero, M.J., Aran Corbella, B., Raya, A., Torrebadella, M., Veiga, A. and Izpisúa Belmonte, J.C. (2009) Generation of induced pluripotent stem cells from cord blood using OCT4 and SOX2. Cell Stem Cell. 5:353-357 NIHMSID # 147979.
Izpisúa Belmonte, J.C., Ellis, J., Hochedlinger, K. and Yamanaka, S. (2009) Induced pluripotent stem cells and reprogramming: seeing the science through the hype. Nature Reviews Genetics. 10:878-883.
Kawamura, T., Suzuki, J., Wang, Y.V., Menendez, S., Batlle, L., Wahl, G. and Izpisúa Belmonte, J.C. (2009) Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature. 460:1140-1144. NIHMSID #134470.
Kan, N., Junghans, D. and Izpisúa Belmonte, J.C. Compensatory growth mechanisms regulated by BMP and FGF signaling pathways mediate liver regeneration in zebrafish after partial hepatectomy. FASEB. 23:3516-3525.
Raya, A., Rodriguez-Piza, I., Guenechea, G., Vassena, R., Navarro, S., Barrero, M.J., Consiglio, A., Rio, P., Sleep, E., Tiscornia, G., Garreta, E., Aasen, T., Veiga, A., Verma, I., Bueren, J. and Izpisúa Belmonte, J.C. (2009) Generation of disease-free hematopoetic progenitors from Fanconi anemia-specific induced pluripotent stem cells. Nature. 460:53-61.
Kelber, J.A., Panopoulos, A.D., Shani, G., Booker, E.C., Belmonte, J.C., Vale, W.W. and Gray, P.C. (2009) Blockade of Cripto binding to cell surface GRP78 inhibits oncogenic Cripto signaling via MAPk/PI3K and Smad2/3 pathways. Oncogene. 28:2324-2336.
Gonzalez, F., Barragan Monasterio, M., Tiscornia, G., Montserrat Pulido, N., Vassena, R., Batlle Morera, L., Rodriguez Piza, I. and Izpsiúa Belmonte, J.C. (2009) Generation of mouse induced pluripotent stem cells by transient expression of a single non-viral polycistronic vector. PNAS. 106:8918-8922.
Beck, C., Izpisúa Belmonte, J.C. and Christen, B. (2009) Beyond Early Development: Xenopus as an emerging model for the study of regenerative mechanisms. Developmental Dynamics. 238:1226-1248
Jopling, C. and Izpisúa Belmonte, J.C. (2009) Cilia-Where Two Wnts Collide. Zebrafish. 6:15-19.
Kawakami, Y., Uchiyama, Y., Rodriguez Esteban, C., Toshiaki, I., Kawakami, H., Marti, M., Kmita, M., Monaghan-Nicols, P., Nishinakamura, R. and Izpisúa Belmonte, J.C. (2008) Sall genes regulate region specific morphogenesis in the limb by modulating Hox activities. Development :136:585-594.
Fink, M., Chu, A., Ruiz-Lozano, P., Callol, C., Izpisúa Belmonte, J.C., Giles, W., Bodmer, R. and Ocorr, K. (2009) A new method for detection and quantification of heartbeat parameters in Drosophila, zebrafish, and embryonic mouse hearts. Biotechniques. 46:101-113.
Rojas-Muñoz, A., Rajadhyksha, S., Gilmour, D., van Bebber, F., Rodríguez-Esteban, C., Nüsslein-Volhard, C., & Izpisúa Belmonte, J.C. (2009) ErbB2 and ErbB3 regulate amputation-induced proliferation and migation during vertebrate regeneration. Developmental Biology:177-190.
Raya, A., Rodriguez-Piza, I., Aran, B., Consiglio, A., Barri, P., Veiga, A., and Izpisúa Belmonte, J.C. (2009) Generation of cardiomyocytes from new human embryonic stem cell lines derived from poor-quality blastocysts. 73rd Cold Spring Harbor Laboratory Symposium. 73:1-9.
Stubbs, J., Oishi, I., Izpisúa Belmonte, J.C. and Kintner, C. (2008) The Forkhead protein, FoxJ1, specified node-like cilia in Xenopus and Zebrafish embryos. Nature Genetics. 40:1454-1460.
Ibanes, M. and Izpisúa Belmonte, J.C. (2008) Left-right asymmetry determination. Wiley Interdisciplinary Reviews: Systems Biology and Medicine. In Press.
Aasen, T., Raya, A., Barrero, M.J., Garreta, E., Consiglio, A., Gonzalez, F., Vassena, R., Bilic, J., Pekarik, V., Tiscornia, G., Edel, M., Boue, S. and Izpisúa Belmonte, J.C. Highly efficient generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology. 26:1276-1284.
Raya, A. and Izpisúa Belmonte, J.C. (2008) Insights into the establishment of left-right asymmetries in vertebrates. BDRC: Embryo Today. 84(2):81-94.
Ibanes, M and Izpisúa Belmonte, J.C. (2008) Theoretical and experimental approaches to understand morphogen gradients. Nature Molecular Systems Biology. 4:176.
Pekarik, V. and Izpisúa Belmonte, J.C. (2008) NFIX-One Gene, Two Knockouts, Multiple Effects. Journal of Biology. 7:29.
Kurpios, N.A., Ibanes, M., Davis, N.M., Lui, W., Katz, T., Martin, J.F., Izpisúa Belmonte, J.C. and Tabin, C.J. (2008) Directional gut looping is mediated by changes in the extracellular matrix and in cell:cell adhesion. PNAS. 105:8499-8506.
Moreno, T.A., Jappelli, R., Brenner, S., Izpisúa Belmonte, J.C., and Kintner, C. (2008) Retinoic Acid Regulation of the Mesp-Ripply Feedback Loop During Vertebrate Segmental Patterning. Developmental Biology. 315:317-330.
Suzuki, A., Sayaka, S., Buscher, D., Izpisúa Belmonte, J.C., and Taniguchi, H. (2008) Tbx3 controls hepatic stem cell fate in liver development by suppressing p19ARF expression. Development. 135:1589-1595
Garcia-Gonzalo, F.R. and Izpisúa Belmonte, J.C. (2008) Albumin-associated Lipids Regulate Human Embryonic Stem Cell Self-Renewal. PLoS ONE. 3:e1384.
Allendorph, G.P., Isaacs, M.J., Kawakami, Y., Izpisúa Belmonte, J.C., Choe, S. (2007) BMP-3 and BMP-6 Structures Illuminate the Nature of Binding Specificity with Receptors. Biochemistry. 46:12238-12247.
Stewart, S., Rojas-Munoz, A., and Izpisúa Belmonte, J.C. (2007) Bioelectricity and epimorphic regeneration. Bioessays. 29(11):1133-1137.
Sahara, S., Kawakami, Y., Izpisúa Belmonte, J.C., O'Leary, D.D.M. (2007) Dual roles of Sp8 on cortical area patterning for anterior or posterior identities. Neuronal Development. 2:10.
Ribeiro, R., Kawakami, Y., Buscher, D., Raya, A., Rodriguez-Leon, J., Morita, M., Rodriguez Esteban, C., Izpisúa Belmonte, J.C. (2007) Tbx2 and Tbx3 regulate the dynamics of cell proliferation during heart regionalization and looping. PLoS One. 4:e398.
Rojas-Munoz, A., Bernad Miana, A., and Izpisúa Belmonte, J.C. (2007) El pez cebra:la navaja suiza de la biologia. Investigacion y Ciencia. 366:62-69.
Zuzarte-Luis, V., Montero, J.A., Kawakami, Y., Izpisúa Belmonte, J.C., and Hurle, J. (2007) Lysosomal cathepsins in embryonic programmed cell death. Developmental Biology. 301:205-217.
Matsui, T., Raya, A., Callol, C., Kawakami, Y., Oishi, I., Rodriguez-Esteban, C., and Izpisúa Belmonte, J.C. (2007) Miles apart-mediated regulation of cell-Fibronectin interaction is required for proper myocardial migration in zebrafish. Nature Clinical Practice Cardiovascular Medicine. 4:S77-S82.
Kawakami, Y., Rodriguez Esteban, C., Raya, M., Kawakami, H., Marti, M., Dubova, I., and Izpisúa Belmonte, J.C. (2006) Wnt/ß-catenin signaling regulates vertebrate limb regeneration. Genes and Development. 20:3232-3237.
Kawakami, Y., Rodriguez-Leon, J., Izpisúa Belmonte, J.C. (2006) The role of TGFßs and Sox9 during limb chondrogenesis. Current Opinion in Cell Biology. 18:723-729
Oishi, I., Kawakami, Y., Raya, A., Callol-Massot, C., Izpisúa Belmonte, J.C. (2006) Regulation of primary cilia formation and left-right patterning in zebrafish by duboraya, a novel mediator of non-canonical Wnt signaling. Nature Genetics. 38:1316-1322
Ibanes, M., Rasskin-Gutman, D., Kawakami, Y., and Izpisúa Belmonte, J.C. (2006) Cell lineage transport: a mechanism for molecular gradient formation. Nature Molecular Systems Biology. 2:57
Suzuki, A.,Raya, A., Kawakami, Y., Morita, M., Matsui, T., Nakashima, K., Gage, F.H.,Rodriguez-Esteban, C., and Izpisúa Belmonte, J.C. (2006) Nanog binds to Smad1and blocks BMP-induced differentiation of embryonic stem cells. PNAS. 103:10294-10299
Soler-Botija,C., Cervera, R.P., Oishi, I., Raya, R.M., Dubova, I., Rodriguez-Esteban, C.,Izpisúa Belmonte, J.C. (2006) Understanding embryonic heart development as atool for cardiac cell based therapy. Annals of Pediatrics. 64:15-22
Weninger,W.J., Geyer, S.H., Mohun, T.J., Rasskin-Gutman, D., Matsui, T., Ribeiro, I.,Costa, L., Izpisúa Belmonte, J.C., Muller, G. B. (2006) High resolutionepiscopic microscopy: a rapid technique for high detailed 3D analysis of geneactivity in the context of tissue architecture and morphology. Anatomy andEmbryology. 211:213-221
Raya, A.,Izpisúa Belmonte, J.C. (2006) Vertebrate left-right asymmetry: a convergence ofdivergences. Nature Reviews Genetics. 7:283-293
Suzuki, A.,Raya, A., Kawakami, Y., Morita, M., Matsui, T., Nakashima, K., Gage, F.H.,Rodriguez-Esteban, C., Izpisúa Belmonte, J.C. (2006) Maintenance of embryonicstem cell pluripotency by Nanog-mediated reversal of mesoderm specification. Nature Clinical Practice Cardiovascular Medicine. 3:S114-S122
Merki, E., Zamora, M., Raya, A., Kawakami, Y., Zhang, X., Burch, J., Kubalak, S., Kaliman, P., IzpisúaBelmonte, J.C., Chien, K., Ruiz-Lozano, P. (2005) Epicardial RXRa is required for myocardial growth and coronary artery formation. PNAS. 102:18455-18460
Leusch, H., Chanda,S.K., Raya, R.M., DeJesus, P.D., Orth, A.P. Walker, J.R., Izpisúa Belmonte,J.C., Schultz, P. (2006) A functional genomics approach to the mode of actionof apratoxin A. Nature Chemical Biology. 2:158-167
Okada, Y.,Takeda, S., Tanaka Y., Izpisúa Belmonte, J.C., and Hirokawa, N. (2005) Mechanism of Ciliated Organ Flow: a Conserved Symmetry Breaking Event inLeft-Right Axis Determination. Cell. 121:633-644
Kawakami,Y., Raya, A., Raya, R.M., Rodriguez-Esteban, C., Izpisúa Belmonte, J.C. (2005). Retinoic acid signaling links left-right asymmetric patterning andbilaterally symmetric somitogenesis in the zebrafish embryo. Nature. Article. 435: 165-171
Correa, R.,Matsui, T., Tergaonkar, V., Rodriguez-Esteban, C., Izpisúa Belmonte, J.C.,Verma, I. (2005) Zebrafish IkB kinase 1 (Ikk1) negatively regulates NF-kBactivity. Current Biology. 15: 1291-1295
Da FontouraCosta, L., Travencolo, B.A.N., Azeredo, A., Beletti, M.E., Rasskin-Gutman, D.,Sternik, G., Izpisúa Belmonte, J.C., Ibanes, M., and Muller, G. (2005) A NovelFiel Approach to 3D Gne Expression Pattern Characterization. Applied PhysicsLetters. 86: 143901-143903
Francisco-Morcillo,J., Sanchez-Calderon, H., Kawakami, Y., Izpisúa Belmonte, J.C.,Hidalgo-Sanchez, M., Martin-Partido, G. (2005) Expression of Fgf19 in thedeveloping eye. Developmental Brain Research. 156:104-109
Kawakami,Y., Tsuda, M., Takahashi, S., Taniguchi, N., Rodriguez-Esteban, C., Zemmyo, M.,Furumatsu, T., Lotz, M., Izpisúa Belmonte, J.C. and Asahara, H. (2005). Transcriptional co-activator PGC-1 regulates chondrogenesis via associationwith Sox 9. PNAS. 102: 2414-2419
Matsui, T.,Raya, A., Kawakami, Y., Callol, C., Capdevila, J., Rodriguez-Esteban, C., andIzpisúa Belmonte, J.C. (2005) Non-canonical Wnt signaling regulates midlineconvergence of organ primordia during zebrafish development. Genes andDevelopment. 19:164-175
Buceta, J., Ibanes, M., Rasskin-Gutman,D., Okada, Y., Hirokawa, N., and Izpisúa Belmonte, J.C. (2005). Nodal CiliaDynamics and the Specification of the Left/Right Axis in Early EmbryoDevelopment. Biophysical Journal. 89:2199-2209.
Rasskin-Gutman, D. and Izpisúa Belmonte,J.C. (2004) Embryos at the core of life, Development 130:5564-5566.
Raya, A., Consiglio, A., Kawakami, Y.,Rodriguez-Esteban, C., and Izpisúa-Belmonte, J.C. (2004) The zebrafish asa model of heart regeneration. Cloning and Stem Cells. 6(4):345-351
Kawakami, Y., Rodriguez Esteban, C.,Matsui, T., Rodriguez-Leon, J., Kato, S. and Izpisúa Belmonte, J.C. (2004)Sp8 and Sp9 regulate Fgf8 expression and limb outgrowth in vertebrateembryos. Development. 31:4763-4774.
Raya, A.and Izpisúa Belmonte, J.C. (2004). Unveiling the establishment of left-rightasymmetry in the chick embryo. Mech. Dev. 121:1043-1054.
Kang, J.S., Oohashi, T., Kawakami, Y.,Bekku, Y., Izpisúa Belmonte, J.C. and Ninomiya, Y. (2004). Characterization ofdermacan, a novel zebrafish lectican gene, expressed in dermal bones. Mechanismsof Development. 121(3):301-312.
Huang Q, Raya A, DeJesus P, Chao SH,Quon KC, Caldwell JS, Chanda SK, Izpisúa-Belmonte JC, Schultz PG. (2004).Identification of p53 regulators by genome-wide functional analysis. Proc.Natl. Acad. Sci. USA. 101(10):3456-3461.
Correa, R.,Tergaonkar, V., Ng, J., Izpisúa-Belmonte, J.C., and Verma, I. (2004) Notochorddifferentiation by the T-box gene ntl in zebrafish is regulated by NFkb. MolecularCell Biology. 24(12):5257-5268.
Raya, A.and Izpisúa Belmonte, J.C. (2004). Sequential transfer of left-rightinformation during vertebrate embryo development. Curr. Op. Gen. and Dev.14:575-581
Rasskin-Gutman, D. andIzpisúa Belmonte, J.C. (2004). Theoretical morphology developmentalasymmetries. BioEssays. 26(4):405-412.
Saez, E., Rosenfeld, J., Livolsi, A.,Lombardo, E., Olson, P., Nelson,M., Banayo, E., Cardiff, R.D., Izpisúa Belmonte, J.C. and Evans, R.M. (2004). PPARg signaling exacerbates mammary gland tumor development. Genesand Development. 18(5):528-540.
Timmerman, L.A., Grego-Bessa, J.,Bertrán, E., Pérez-Pomares, J.M., Diez, J., Aranda, S., Palomo, S., Raya, A.,McCormick, F., Izpisúa Belmonte, J.C. and de la Pompa, J.L. (2004). Notchpromotes epithelial-mesenchymal transitions during heart development andtransformation. Genes and Development. 18(1):99-115
Raya, A., Kawakami, Y., Rodriguez-Esteban,C., Ibañes, M., Rasskin-Gutman, D., Rodriguez-León, J., Büscher, D.,Feijó, J.A. and Izpisúa Belmonte, J.C. (2004). Notch activity acts as asensor for extracellular calcium during vertebrate left-rightdetermination. Nature. 427:121-128. Article.
Raya, A., Koth, C.M., Büscher, D.,Kawakami, Y., Itoh, T., Raya, R.M., Sternik, G., Tsai, H.-J.,Rodriguez-Esteban, C. and Izpisúa Belmonte, J.C. (2003). Activation of Notchsignaling pathway precedes heart regeneration in zebrafish. Proc. Natl.Acad. Sci. USA, Special Supplement on Stem Cells and the Future of Regenerative Medicine. 100:11889-11895.
Groppe, J., Greenwald, J., Wiater, E.,Rodriguez-Leon, J., Economides, A.N., Kwiatkowski, W., Baban, K., Affolter, M.,Vale, W.W., Izpisúa Belmonte, J.C. and Choe, S. (2003). Structural basis ofBMP signaling inhibition by Noggin, a novel twelve-membered cystine knotprotein. The Jnl. of Bone and Joint Surgery 85-A, Suppl. 3:52-58.
Raya, A., Kawakami, Y.,Rodriguez-Esteban, C., Büscher, D., Koth, C.M., Itoh, T., Morita, M.,Raya, R.M., Dubova, I., Grego Bessa, J., de la Pompa, J.L. and Izpisúa Belmonte, J.C. (2003). Notch activity induces Nodal expression andmediates the establishment of left-right asymmetry in vertebrate embryos. GenesDev. 17:1213-1218.
Kawakami, Y., Rodriguez-Leon, J., Koth,C.M., Büscher, D., Itoh, T., Raya, A., Ng, J.K., Rodriguez Esteban, C.,Takahashi, S., Henrique, D., Schwarz, M.F., Asahara, H. and Izpisúa Belmonte, J.C. (2003). MKP3 mediates the cellular response to FGF8signalling in the vertebrate limb. Nature Cell Biology 5:513-519.Article
Groppe, J., Greenwald, J., Wiater, E.,Rodriguez-Leon, J., Economides, A.N., Kwiatkowski, W., Affolter, M., Vale,W.W., Izpisúa Belmonte, J.C. and Choe, S. (2002). Structural basis of BMPsignalling inhibition by the cystine knot protein Noggin. Nature 420:636-642.Article
Belmonte, J.C. (2002). The limb identitygene Tbx5 promotes limb initiation by interacting with Wnt-2band Fgf-10. Development 129:5161-5170.
Ng, J., Kawakami, Y., Büscher, D., Raya,A., Itoh, T., Koth, C., Rodríguez Esteban, C., Rodriguez Leon, J., Garrity, D.M., Fishman, M.C. and Izpisúa
Hurle, J.M.and Izpisúa Belmonte, J.C. (Ed.). 2002. Limb Development, Special Issue. Intl.Jnl. of Dev. Biol., Volume 46, Issue No. 7.
Diaz Trelles, R., Rodriguez Leon, J., Kawakami, Y., Simoes, S. and Izpisúa Belmonte, J.C. (2002). Expression of thechick vascular endothelial growth factor D gene during limbdevelopment. Mechanisms of Development 116:239-242.
Capdevila, J. and Izpisúa Belmonte, J.C.(2001). Patterning mechanisms controlling vertebrate limb development. Ann.Rev. Cell Dev. Biol. 17:87-132.
Rodriguez-Esteban, C., Raya, A.,Capdevila, J. and Izpisúa Belmonte, J.C. (2001). Cómo distingue el cuerpola izquierda de la derecha? Investigacion y Ciencia 300:62-69.
Mukhopadhyay, M., Shtrom, S.,Rodriguez-Esteban, C., Chen, L., Tsukui, T., Gomer, L., Dorward, D.W.,Glinka, A., Grinberg, A., Huang, S.-P., Niehrs, C., Izpisúa Belmonte, J.C.and Westphal, H. (2001). Dickkopf1 is required for embryonic headinduction and limb morphogenesis in the mouse. Developmental Cell 1:423-434.
Tavares, A.T., Izpisúa Belmonte, J.C.and Rodriguez-Leon, J. (2001). Developmental expression of chick Twistand its regulation during limb patterning. Intl. Jnl. of Dev.Biol. 45:707-713.
Rodriguez-Esteban, C., Capdevila, J.,Kawakami, Y. and Izpisúa Belmonte, J.C. (2001). Wnt signaling and PKAcontrol Nodal expression and left-right determination in the chickembryo. Development 128:3189-3195.
Sharma, K. and Izpisúa Belmonte, J.C.(2001). Development of the limb neuromuscular system. Curr. Opin. CellBiol. 13:204-210.
Kawakami, Y., Capdevila, J., Büscher,D., Itoh, T., Rodriguez-Esteban, C., and Izpisúa Belmonte, J.C. (2001). Wnt signals control FGF-dependent limb initiation and AER induction in thechick embryo. Cell 104:891-900.
Capdevila, J. and Izpisúa Belmonte, J.C.(2000). Perspectives on the evolutionary origin of tetrapod limbs. Jnl.of Exp. Zool. 288:287-303.
Ruiz-Lozano, P., Ryan, A.K. and Izpisúa Belmonte, J.C. (2000). Left-right axis determination. Trends inCardiovascular Med. 10:258-262.
Liang, J.O., Etheridge,A., Hantsoo, L., Rubinstein, A.L., Nowak, S.J., Izpisúa Belmonte, J.C., and Halpern, M.E. (2000). Asymmetric Nodal signaling in the zebrafish diencephalons positionsthe pineal organ. Development 127:5101-5112.
Ryan, A.K. and Izpisúa Belmonte, J.C. (2000). Establishing a left-right axis in the embryo. IUBMB Life 50:1-11.
Tavares, A.T., Tsukui, T., and Izpisúa Belmonte, J.C. (2000). Evidence that members of the Cut/Cux/CDP familymay be involved in AER positioning and polarizing activity during chicklimb development. Development 127:5133-5144.
Yokoyama, H., Yonei-Tamura, S., Endo,T., Izpisúa Belmonte, J.C., Tamura, K. and Ide, H. (2000). Mesenchymewith Fgf-10 expression is responsible for regenerative capacity in Xenopuslimb buds. Developmental Biol. 219:18-29.
Capdevila, J., Vogan, K.J., Tabin, C.J.and Izpisúa Belmonte, J.C. (2000). Mechanisms of left-right determinationin vertebrates. Cell 101:9-21.
Capdevila, J. and Izpisúa Belmonte, J.C.(2000). Knowing left from right: the molecular basis of lateralitydefects. Mol. Med. Today 6:112-118.
Tamura, K., Yonei-Tamura, S. and Izpisúa Belmonte, J.C. (1999). Differential expression of Tbx4 and Tbx5in Zebrafish fin buds. Mech. Dev. 87:181-184.
Capdevila, J., Tsukui, T.,Rodriguez-Esteban, C., Zappavigna, V. and Izpisúa Belmonte, J.C. (1999). Control of vertebrate limb outgrowth by the proximal factor Meis2 anddistal antagonism of BMPs by Gremlin. Mol. Cell 4:839-849.
Tamura, K., Yonei-Tamura, S. and Izpisúa Belmonte, J.C. (1999). Molecular basis of left-right asymmetry. Dev.Growth Differ. 41:645-656.
Tsukui, T., Capdevila, J., Tamura, K.,Ruiz-Lozano, P., Rodriguez-Esteban, C., Yonei-Tamura, S., Magallon, J.,Chandraratna, R.A.S., Chien, K., Blumberg, B., Evans, R.M. and Izpisúa Belmonte, J.C. (1999). Multiple left-right asymmetry defects in Shh^-/-mutant mice unveil a convergence of the Shh and Retinoic Acid pathwaysin the control of Lefty-1. Proc. Natl. Acad. Sci. USA 96:11376-11381.
Tavares, A., Capdevila, J. and Izpisúa Belmonte, J.C. (1999). Transcription factors during limb development. ScientificAmerican (Sp. edit.) 4, 30-32
Lin, C.R., Kioussi, C.,O'Connell, S., Briata, P., Szeto, D., Liu, F., Izpisúa Belmonte, J.C. andRosenfeld, M.G. (1999). Pitx2 regulates lung asymmetry, cardiac positioningand pituitary and tooth morphogenesis. Nature 401:279-282.
Rodriguez-Esteban, C.,Capdevila, J., Economides, A.N., Pascual, J., Ortiz, A. and Izpisúa Belmonte,J.C. (1999). The novel Cer-like protein Caronte mediates the establishment ofembryonic left-right asymmetry. Nature 401:243-251. Article
Yamada, G., Nakamura, S., Fukuzaki, K.,Izumi, H., Horai, N., Nagata, R., Minami, T., Tohno, Y., Suzuki, K.,Haraguchi, R., Miyado, K., Toyoda, T., Izpisúa Belmonte, J.C., Maruyama,I. and Kitajima, I. (1999). Dysregulation of trace element composition inovariectomized cynomolgus monkey bones. Cell. & Mol. Biol. 44:1205-1213.
Garcia-Domingo, D., Leonardo, E.,Grandien, A., Martinez, P., Albar, J.P., Izpisúa Belmonte, J.C. andMartinez-A., C. (1999). DIO-1 is a gene involved in onset ofapoptosis in vitro, whose misexpression disrupts limb development. Proc.Natl. Acad. Sci. USA 96:7992-7997.
Bach, I.,Rodriguez-Esteban, C., Carriere, C., Bhushan, A., Krones, A., Rose, D.W.,Glass, C.K., Andersen, B., Izpisúa Belmonte, J.C. and Rosenfeld, M.G. (1999). RLIM inhibits functional activity of LIM homeodomain transcription factors viarecruitment of the histone deacetylase complex. Nature Genet. 22:394-399.
Huang, R., Zhi, Q., Izpisúa Belmonte,J.C., Christ, B. and Ketan, P. (1999). Origin and development of theavian tongue muscles. Anat. Embryol. 200:137-152.
Capdevila, J. and Izpisúa Belmonte, J.C.(1999). Extracellular modulation of the Hedgehog,Wnt and TGF-b signalling pathways during embryonicdevelopment. Curr. Opin. Genet. Dev. 9:427-433.
Merino, R., Macias, D.,Gañan, Y., Rodriguez-Leon, J., Economides, A.N., Rodriguez-Esteban, C., Izpisúa Belmonte, J.C. and Hurle, J.M. (1999). Control of digit formation by activinsignalling. Development 126:2161-2170.
Izpisúa Belmonte, J.C. (1999). How thebody tells left from right. Scientific American 280:46-51.
Li, Q., Lu, Q., Hwang, J.Y., Büscher,D., Lee, K.-F., Izpisúa Belmonte, J.C. and Verma, I.M. (1999). IKK1-deficient mice exhibit abnormal development of skin and skeleton. GenesDev. 13:1322-1328.
Rodriguez-Esteban, C., Tsukui, T.,Yonei, S., Magallon, J., Tamura, K. and Izpisúa Belmonte, J.C. (1999). The T-Box genes Tbx4 and Tbx5 regulate limb outgrowth andidentity. Nature 398:814-818.
Büscher, D. and Izpisúa Belmonte, J.C.(1999). Muscle development during vertebrate limb outgrowth. Cell & Tissue Res. 296:131-139.
.Rincon-Limas, D.E., Lu, C.-H., Canal, I., Calleja, M., Rodriguez Esteban, C., Izpisúa Belmonte, J.C. and Botas, J. (1999). Conservation of the expression and function of apterous orthologsin Drosophila and mammals. Proc. Natl. Acad. Sci. USA 96:2165-2170
Yonei-Tamura, S., Tamura, K., Tsukui, T.and Izpisúa Belmonte, J.C. (1999). Spatially and temporally-restrictedexpression of two T-box genes during zebrafish embryogenesis. Mech.Dev. 80:219-221.
Szeto, D.P., Rodriguez-Esteban, C.,Ryan, A.K., O'Connell, S.M., Liu, F., Kioussi, C., Gleiberman, A.S.,Izpisúa Belmonte, J.C. and Rosenfeld, M.G. (1999). Role of the Bicoid-related homeodomain factor Pitx1 in specifying hindlimb morphogenesisand pituitary development. Genes Dev. 13:484-494.
Torok, M.A., Gardiner, D.M., Izpisúa Belmonte, J.C. and Bryant, S.V. (1999). Sonic Hedgehog (shh) expressionin developing and regenerating Axolotl limbs. J. of Exp. Zool. 284:197-206.
Ng, J.K., Tamura, K., Büscher, D. andIzpisúa Belmonte, J.C. (1999). Outgrowth and patterning of the vertebratelimb. Molecular and cellular basis of pattern formation during vertebrate limb development. Current Topics in Dev. Biol. 41:37-66.
Takahashi, M., Tamura, K., Büscher, D.,Masuya, H., Yonei-Tamura, S., Matsumoto, K., Naitoh-Matsuo, M., Takeuchi,J., Ogura, K., Shiroishi, T., Ogura, T. and Izpisúa Belmonte, J.C.(1998). The role of Alx-4 in the establishment of anteroposteriorpolarity during vertebrate limb outgrowth. Development 125:4417-4425.
Rodriguez-Esteban, C., Schwabe, J.W.R.,De La Peña, J., Rincon-Limas, D.E., Magallon, J., Botas, J. and Izpisúa Belmonte, J.C. (1998). Lhx2, a vertebrate homologue of apterous,regulates vertebrate limb outgrowth. Development 125:3925-3934.
Ryan, A., Blumberg, B.,Rodriguez-Esteban, C., Yonei-Tamura, S., Tamura, K., Tsukui, T., De LaPeña, J., Sabbagh, W., Greenwald, J., Choe, S., Norris, D.P., Robertson,E.J., Evans, R.M., Rosenfeld, M.G. and Izpisúa Belmonte, J.C. (1998). Pitx2determines left-right asymmetry of internal organs in vertebrates. Nature 394:545-551. Article
Schwabe, J.W.R., Rodriguez-Esteban, C.and Izpisúa Belmonte, J.C. (1998). Limbs are moving...where are they going? Trends in Genetics 14:229-235.
Isaac, A., Rodriguez-Esteban, C., Ryan,A., Altabef, M., Tsukui, T., Patel, K., Tickle, C. and Izpisúa Belmonte,J.C. (1998). Tbx genes and limb identity in chick embryo development. Development 125:1867-1875.
Kengaku, M., Capdevila, J., Rodriguez-Esteban,C., De La Peña, J., Johnson, R.L., Izpisúa Belmonte, J.C. and Tabin, C.J. (1998). Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud. Science 280:1274-1277.
Capdevila, J., Rodriguez-Esteban, C. andIzpisúa Belmonte, J. C. (1998). Molecular architecture of the vertebrate limb. Scientific American 12:23-37 (Sp. edit.).
Kanegae, Y., Tavares, A.T., Izpisúa Belmonte, J.C. and Verma, I.M. (1998). Role of Rel/NF-KB transcription factors during the outgrowth of the vertebrate limb. Nature 392:611-614.
Heanue, T.A., Johnson, R.L., Izpisúa Belmonte, J.C., Stern, C.D., DeRobertis, E.M. and Tabin, C.J. (1997). Goosecoidmisexpression alters the morphology and Hox gene expression of the developing chick limb bud. Mech. Dev. 69:31-37.
Schwabe, J.W.R.,Rodriguez-Esteban, C., De La Peña, J., Tavares, A., Ng, J., Banayo, E.M., Foys,B., Eshelman, B., Magallon, J., Tam, R. and Izpisúa Belmonte, J.C. (1997). Outgrowth and patterning of the vertebrate limb. Cold Spring Harbor Symposia on Biology, Vol. LXII, pp. 431-435.
Pfeffer, P., De Robertis, E. and Izpisúa Belmonte, J. C. (1997). Crescent, a novel chick gene encoding a Frizzled-like Cysteine-Rich Domain, is expressed in anterior regionsduring early embryogenesis. Int. J. Dev. Biol. 41(3):449-458.
Lemaire, L., Röser, T., Izpisúa Belmonte, J. C. and Kessel, M. (1997). Segregating expression domains of two goosecoid genes during the transition from gastrulation to neurulationin chick embryos. Development 124:1443-1452.
Rodriguez-Esteban, C., Schwabe, J.W.R.,De La Peña, J., Foys, B., Eshelman, B. and Izpisúa Belmonte, J.C. (1997). Radical fringe positions the apical ectodermal ridge at the dorsoventral boundary of the vertebrate limb. Nature 386:360-366. Article
Rodriguez, C., Kos, R., Macias, D.,Abbott, U. K. and Izpisúa Belmonte, J. C. (1996). Shh, HoxD, Bmp-2, andFgf-4 gene expression during development of the polydactylous talpid2,diplopodia1, and diplopodia4 mutant chick limb buds. Dev.Genetics 19:26-32.
Ros, M., Lopez Martinez, A., Simandl, B.K., Rodriguez, C., Izpisúa Belmonte, J. C., Dahn, R. and Fallon, J.(1996). The limb field mesoderm determines initial limb budanteroposterior asymmetry and budding independent of sonic hedgehogor apical ectodermal gene expressions. Development 122:2319-2330.
Vogel, A., Rodriguez, C. and Izpisúa Belmonte, J. C. (1996). Involvement of FGF-8 in initiation, outgrowth,and patterning of the vertebrate limb. Development 122:1737-1750.
Van der Hoeven, F., Sordino, P.,Fraudeau, N., Izpisúa Belmonte, J.C. and Duboule, D. (1996). Teleost HoxDand HoxA genes: comparison with tetrapods and functional evolution of the HOXD complex. Mech. Dev. 54:9-21.
Ogura, T., Alvarez, S., Vogel, A.,Rodriguez, C., Evans, R. and Izpisúa Belmonte, J.C. (1996). Evidence thatShh cooperates with a retinoic acid inducible co-factor to establish ZPA-like activity. Development 122:537-542.
Vogel, A., Rodriguez, C., Warnken W. andIzpisúa Belmonte, J. C. (1995). Dorsal cell fate specified by chick Lmx1during vertebrate limb development. Nature 378:716-720.
Hardy, A., Richardson, M. K., Philippa,H., Francis-West, P. H., Rodriguez, C., Izpisúa Belmonte, J. C., Duprez,D. and Wolpert, L. (1995). Gene expression, polarizing activity andskeletal patterning in reaggregated hind limb mesenchyme. Development 121:4329-4337.
Sucov, H., Izpisúa Belmonte, J. C.,Gañan, Y. and Evans R. (1995). Mouse embryos lacking RXRa are resistantto retinoic-acid-induced limb defects. Development 121:3997-4003.
Cohn, M., Izpisúa Belmonte, J. C., Abud, H., Heath, J. K. and Tickle, C. (1995). FibroblastGrowth Factors induce additional limb development from the flank of chick embryos. Cell 80:739-746.
Francis-West, P. H., Robertson, K., Ede,D. A., Rodriguez, C., Izpisúa Belmonte, J.C., Houston, B., Burt, D. W.,Gribbin, C., Brickell, P. M. and Tickle, C. (1995). Expression of genesencoding bone morphogenetic proteins and sonic hedgehog in Talpid (ta3)limb buds: their relationships in the signaling cascade involved in limb patterning. Dev. Dynamics 203:187-197.
Fjose, A., Izpisúa Belmonte, J. C.,Fromental, C. and Duboule, D. (1994). Expression of the zebrafish gene hlx-1in the prechordal plate and during CNS development. Development 120:71-81.
Olivo, J., Izpisúa Belmonte, J. C.,Tickle, C., Boulin, C. and Duboule, D. (1993). Reconstruction fromserial sections: a tool for developmental biology. Application to Hoxgenes expression in chicken wing buds. BioImaging 1:115-158.
Dollé, P., Izpisúa Belmonte, J.C.,Brown, J., Tickle, C. and Duboule, D. (1993). Hox genes and the morphogenesis of the vertebrate limb. Prog. Clin. Biol. Res. 383A:11-20.
Izpisúa Belmonte, J. C., De Robertis,E., Storey, K. and Stern, C. (1993). The homeobox gene goosecoid andthe origin of organizer cells in the early chick blastoderm. Cell 74:645-659.
Morgan, B., Izpisúa Belmonte, J. C.,Duboule, D. and Tabin C. (1992). Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations. Nature 358:236-239.
Izpisúa-Belmonte, J. C.and Duboule, D. (1992). Homeobox genes and pattern formation in the vertebrate limb. Dev. Biol. 152:26-36.
Bastian, H., Gruss, P., Duboule, D. andIzpisúa Belmonte, J.C. (1992). The murine even-skipped-like gene Evx-2is closely linked to the Hox-4 complex, but is transcribed in the opposite direction. Mammalian Genome 3:241-243.
Izpisúa Belmonte, J. C., Brown, J. M., Crawley, D., Duboule, D. and Tickle, C. (1992). HOX-4 gene expression in mouse/chicken heterospecific grafts of signaling regions to limb buds reveals similarities in patterning mechanisms. Development 115:553-560.
Renucci, A., Zappavigna, V., Zakany, J.,Izpisúa Belmonte, J. C., Bürki, K. and Duboule, D. (1992). Comparison ofmouse and human HOX-4 complexes defines conserved sequences involved in the regulation of Hox-4.4. EMBO J. 11:1459-1468.
Izpisúa Belmonte, J.C., Brown, J.M.,Duboule, D. and Tickle, C. (1992). Expression of HOX-4 genes in the chickwing links pattern formation to the epithelial-mesenchymal interactions that mediate growth. EMBO J. 11:1451-1457.
Izpisúa Belmonte, J. C., Ede, D., Tickle, C. and Duboule, D. (1992). The misexpression of posterior HOX-4 genes in talpid(ta3) mutant wings correlates with the absence of anteroposteriorpolarity. Development 114:959-963.
Izpisúa Belmonte, J. C., Tickle, C.,Dollé, P. and Duboule, D. (1991). HOX-4 genes and the molecular basis ofvertebrate limb pattern formation. Seminars in Dev. Biol. 2:385-391.
Dollé, P., Izpisúa Belmonte, J. C.,Boncinelli, E. and Duboule, D. (1991). The Hox-4.8 gene is localized at the 5' extremity of the HOX-4 complex and is expressed at the posteriorend of the body during development. Mech. Dev. 36(1-2):3-13.
Dollé, P., Izpisúa Belmonte, J. C., Brown, J., Tickle, C. and Duboule, D. (1991). HOX-4 genes and the morphogenesis of mammalian genitalia. Genes Dev. 5:1767-1776.
Zappavigna, V., Renucci, A., Izpisúa Belmonte, J. C., Urier, G., Peschle, C. and Duboule, D. (1991). HOX4 genes encode transcription factors with potential auto- andcross-regulatory capacities. EMBO J. 10:4177-4187.
Izpisúa Belmonte, J.C., Falkenstein, H.,Dollé, P., Renucci, A. and Duboule, D. (1991). Murine genes related tothe Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body. EMBO J. 10:2279-2289.
Izpisúa Belmonte, J.C., Tickle, C.,Dollé, P., Wolpert, L. and Duboule, D. (1991). Expression of the homeoboxHox-4 genes and the specification of position in chick wing development. Nature 350:585-589. Article
Izpisúa-Belmonte, J.C., Dollé, P.,Renucci, A., Zappavigna, V., Falkenstein, H. and Duboule, D. (1990). Primary structure and embryonic expression pattern of the mouse Hox-4.3homeobox gene. Development 110:733-745.
Dollé, P., Izpisúa Belmonte, J. C.,Falkenstein, H., Renucci, A. and Duboule, D. (1989). Coordinate expression of the murine Hox-5 complex homeobox-containing genes duringlimb pattern formation. Nature 342:767-772. Article
Bordoni A, Biagi PL, Parenti Castelli G,Hrelia S, Rossi CA, Lercker G, Izpisúa JC, Barber T, Cabo J, a Lenaz G. (1989). Effect of a hyperlipidic diet on lipid composition, fluidity, and Na+-K+-ATPase activity of rat erythrocyte membranes. Membrane Biochem. 8:11-18.
Izpisúa JC, Barber T, Cabo J, Hrelia S,Rossi CA, Parenti Castelli G, Lercker G, Biagi PL, Bordoni A, Lenaz G.Lipid composition, fluidity and enzymatic activities of rat liver plasmaand mitochondrial membranes in dietary obese rats. Int. J. Obesity 13:531-542.

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