Unidades docentes

  1. Portada
  2. Genetics Unit
  3. Research
  4. Developmental genetics in mice

Developmental genetics in mice

Researcher: Delgado Carceller, Irene

 

In the lab, we are interested in understanding the cellular and molecular bases that regulate embryonic development, in particular limb development. The limb bud begins to form as protrusion on the flank of the embryo, and this bud is going to grow along the three spatial axes under the control of various signaling centers. Proper coordination among all the factors and signaling pathways involved will result in the formation of a correct skeletal pattern, while any disruption will generate incorrect patterns. In the laboratory, we study the role Meis transcription factors in these processes. Meis proteins form a gradient along the limb bud proximo-distal axis and are able to interpret FGF signals, establishing a mechanism of positional information for the cell. In other words, the amount of Meis in the cell is a readout of the amount of FGF and therefore of its positional localization within the proximo-distal axis of the developing limb. Moreover, through the study of knock-out embryos for these genes, we have described that they regulate Hox genes expression which are key factors during embryo development. The phenotypic, molecular, and cellular characterization of these knock-out embryos allows us to elucidate the role of Meis genes throughout development.

 

Sección de un primordio de extremidad mostrando en rosa la proteína Meis. En el aumento se aprecian los ditintos niveles de Meis en cada célula.

Section of a limb primordium showing the Meis protein in pink. The zoom in shows the different levels of Meis in each cell.

 

Limbs that develop in the absence of Meis transcription factors, which are responsible for interpreting cellular positional information, do not develop a correct skeletal pattern (phocomelic limb).

 

PUBLICATIONS

  • Irene Delgado; Giovanna Giovinazzo; Susana Temiño; Yves Gauthier; Aurelio Balsalobre; Jacques Drouin; Miguel Torres. Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors. Nature Communications. 12 - 3086 (2021),

  • Irene Delgado; Alejandra C López Delgado; Alberto Roselló Díez; Giovanna Giovinazzo; Vanessa Cadenas; Laura Fernández de Manuel; María C Montoya; Fátima Sánchez Cabo; Matthew J. Anderson; Mark Lewandoski; Miguel Torres. Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb. Science Advances. 6 - 23, 03/06/2020.

  • Alejandra C López Delgado; Irene Delgado; Vanessa Cadenas; Fátima Sánchez Cabo; Miguel Torres. Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid. Development. 148 (1), 04/01/2021.

  • Maria Sanz Navarro; Irene Delgado; Miguel Torres; Tuija Mustonen; Frederic Michon; DavidP. Rice. Dental Epithelial Stem Cells Express the Developmental Regulator Meis. Dental Epithelial Stem Cells Express the Developmental Regulator Meis1. Frontiers in Physiology. 10, 12/03/2019

  • Irene Delgado; Miguel Torres. Coordination of limb development by crosstalk among axial patterning pathways. Developmental Biology. 429 - 2, pp. 382 - 386. 15/09/2017

  • Irene Delgado Carceller; Miguel Torres Sánchez.Gradients, waves and timers, an overview of limb patterning models. Seminars in Cell & Developmental Biology. 49, pp. 109 - 115. 01/2016

  • Patricia Saiz López; Kavitha Chinnaiya; Víctor Campa Fernández; Irene Delgado Carceller; Maria Ángeles Ros Lasierra; Matthew Towers. An intrinsic timer specifies distal structures of the vertebrate limb. Nature Communications. 6:8108, 18/09/2015.

  • Mónica González Lázaro; Alberto Roselló Díez; Irene Delgado; Laura Carramolino; María Angeles Sanguino; Giovanna Giovinazzo; Miguel Torres. Two New Targeted Alleles for the Comprehensive Analysis of Meis1 Functions in the Mouse. Genesis. 52, pp. 967 - 975. 11/11/2014

  • Endika Haro Gabikagogeaskoa; Irene Delgado; Marisa Junco; Yoshihiko Yamada; Ahmed Mansouri; KerbyC. Oberg; Marian Ros. Sp6 and Sp8 transcription factors control AER formation and dorsoventral patterning in limb development. PLOS Genetics. 10 (8), 28/08/2014

  • Alberto Roselló Díez; CarlosG. Arques; Irene Delgado; Giovanna Giovinazzo; Miguel Torres. Diffusible signals and epigenetic timing cooperate in late proximo-distal limb patterning. Development. 141 - 7, pp. 1534 - 1543. 01/04/2014

  • Malcolm Fisher; Helen Downie; Monique C.M. Welten; Irene Delgado; Andrew Bain; Thorsten Planzer; Adrian Sherman; Helen Sang; Cheryll Tickle. Comparative analysis of 3D expression patterns of Hoxd13, Tbx2, Tbx3, Sall1, Sall3 genes in the developing chick wing and relationship to cell lineages contributing to individual digits. PLOS ONE. 6 - 4, 22/04/2011

  • Ana Talamillo*; Irene Delgado*; Takashi Nakamura; Susana de Vega; Yasuo Yoshitomi; Fernando Unda; Walter Birchmeier; Yoshi Yamada; Maria Angeles Ros. *co-first authors. Role of Epiprofin, a zinc-finger transcription factor, in limb development. Developmental Biology. 337 - 2, pp. 363 - 374. 15/01/2010

  • Jenna Galloway*; Irene Delgado*; Maria Angeles Ros; Cliff Tabin.   *co-first authors. A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning. Nature. 460 - 7253, pp. 400 - 404. 16/07/2009

  • Irene Delgado; Elena Domínguez Frutos; Thomas Schimmang; Maria Angeles Ros. The incomplete inactivation of Fgf8 in the limb ectoderm affects the morphogenesis of the anterior autopod through BMP-mediated cell death. Developmental Dynamics. 237 - 3, pp. 649 - 658. 01/03/2008