Person: Torres, Miguel
Loading...
First Name
Miguel
Last Name
Torres
Institution
CNIC
Centrre
CNIC Organization
CNIO Organization
Institute
Identifiers
6 results
Search Results
Now showing 1 - 6 of 6
Publication Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid.(The Company of Biologists, 2021-01-04) López-Delgado, Alejandra C; Delgado, Irene; Cadenas, Vanessa; Sanchez-Cabo, Fatima; Torres, Miguel; Ministerio de Ciencia, Innovación y Universidades (España); Instituto de Salud Carlos III; Comunidad de Madrid (España); Fundación ProCNIC; Ministerio de Economía y Competitividad (España)Vertebrate axial skeletal patterning is controlled by co-linear expression of Hox genes and axial level-dependent activity of HOX protein combinations. MEIS transcription factors act as co-factors of HOX proteins and profusely bind to Hox complex DNA; however, their roles in mammalian axial patterning remain unknown. Retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors; however, whether this role is related to MEIS/HOX activity remains unknown. Here, we study the role of Meis in axial skeleton formation and its relationship to the RA pathway in mice. Meis elimination in the paraxial mesoderm produces anterior homeotic transformations and rib mis-patterning associated to alterations of the hypaxial myotome. Although Raldh2 and Meis positively regulate each other, Raldh2 elimination largely recapitulates the defects associated with Meis deficiency, and Meis overexpression rescues the axial skeletal defects in Raldh2 mutants. We propose a Meis-RA-positive feedback loop, the output of which is Meis levels, that is essential to establish anterior-posterior identities and patterning of the vertebrate axial skeleton.Publication Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development.(Nature Publishing Group, 2024-05) Dvoretskova, Elena; Ho, May C; Kittke, Volker; Neuhaus, Florian; Vitali, Ilaria; Lam, Daniel D; Delgado, Irene; Feng, Chao; Torres, Miguel; Winkelmann, Juliane; Mayer, Christian; Unión Europea. Comisión Europea. European Research Council (ERC); Unión Europea. Comisión Europea. H2020The mammalian telencephalon contains distinct GABAergic projection neuron and interneuron types, originating in the germinal zone of the embryonic basal ganglia. How genetic information in the germinal zone determines cell types is unclear. Here we use a combination of in vivo CRISPR perturbation, lineage tracing and ChIP-sequencing analyses and show that the transcription factor MEIS2 favors the development of projection neurons by binding enhancer regions in projection-neuron-specific genes during mouse embryonic development. MEIS2 requires the presence of the homeodomain transcription factor DLX5 to direct its functional activity toward the appropriate binding sites. In interneuron precursors, the transcription factor LHX6 represses the MEIS2-DLX5-dependent activation of projection-neuron-specific enhancers. Mutations of Meis2 result in decreased activation of regulatory enhancers, affecting GABAergic differentiation. We propose a differential binding model where the binding of transcription factors at cis-regulatory elements determines differential gene expression programs regulating cell fate specification in the mouse ganglionic eminence.Publication Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors.(Nature Publishing Group, 2021-05-25) Delgado, Irene; Giovinazzo, Giovanna; Temiño, Susana; Gauthier, Yves; Balsalobre, Aurelio; Drouin, Jacques; Torres, Miguel; Ministerio de Ciencia e Innovación (España); Fundación ProCNICMeis1 and Meis2 are homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Elimination of Meis genes after limb induction has shown their role in limb proximo-distal patterning; however, limb development in the complete absence of Meis function has not been studied. Here, we report that Meis1/2 inactivation in the lateral plate mesoderm of mouse embryos leads to limb agenesis. Meis and Tbx factors converge in this function, extensively co-binding with Tbx to genomic sites and co-regulating enhancers of Fgf10, a critical factor in limb initiation. Limbs with three deleted Meis alleles show proximal-specific skeletal hypoplasia and agenesis of posterior skeletal elements. This failure in posterior specification results from an early role of Meis factors in establishing the limb antero-posterior prepattern required for Shh activation. Our results demonstrate roles for Meis transcription factors in early limb development and identify their involvement in previously undescribed interaction networks that regulate organogenesis.Publication Dental Epithelial Stem Cells Express the Developmental Regulator Meis1(Frontiers Media, 2019) Sanz-Navarro, Maria; Delgado, Irene; Torres, Miguel; Mustonen, Tuija; Michon, Frederic; Rice, David P; Minerva Foundation; University of Helsinki (Finlandia); Finlands Akademi (Finlandia)MEIS1 is a key developmental regulator of several organs and participates in stem cell maintenance in different niches. However, despite the murine continuously growing incisor being a well described model for the study of adult stem cells, Meis1 has not been investigated in a dental context. Here, we uncover that Meis1 expression in the tooth is confined to the epithelial compartment. Its expression arises during morphogenesis and becomes restricted to the mouse incisor epithelial stem cell niche, the labial cervical loop. Meis1 is specifically expressed by Sox2+ stem cells, which give rise to all dental epithelial cell lineages. Also, we have found that Meis1 in the incisor is coexpressed with potential binding partner Pbx1 during both embryonic and adult stages. Interestingly, Meis2 is present in different areas of the forming tooth and it is not expressed by dental epithelial stem cells, suggesting different roles for these two largely homologous genes. Additionally, we have established the expression patterns of Meis1 and Meis2 during tongue, hair, salivary gland and palate formation. Finally, analysis of Meis1-null allele mice indicated that, similarly, to SOX2, MEIS1 is not essential for tooth initiation, but might have a role during adult incisor renewal.Publication Molecular mechanism of synovial joint site specification and induction in developing vertebrate limbs.(The Company of Biologists, 2023-07-01) Yadav, Upendra S; Biswas, Tathagata; Singh, Pratik N; Gupta, Pankaj; Chakraborty, Soura; Delgado, Irene; Zafar, Hamim; Capellini, Terence D; Torres, Miguel; Bandyopadhyay, Amitabha; Ministerio de Ciencia e Innovación (España)The vertebrate appendage comprises three primary segments, the stylopod, zeugopod and autopod, each separated by joints. The molecular mechanisms governing the specification of joint sites, which define segment lengths and thereby limb architecture, remain largely unknown. Existing literature suggests that reciprocal gradients of retinoic acid (RA) and fibroblast growth factor (FGF) signaling define the expression domains of the putative segment markers Meis1, Hoxa11 and Hoxa13. Barx1 is expressed in the presumptive joint sites. Our data demonstrate that RA-FGF signaling gradients define the expression domain of Barx1 in the first presumptive joint site. When misexpressed, Barx1 induces ectopic interzone-like structures, and its loss of function partially blocks interzone development. Simultaneous perturbations of RA-FGF signaling gradients result in predictable shifts of Barx1 expression domains along the proximo-distal axis and, consequently, in the formation of repositioned joints. Our data suggest that during early limb bud development in chick, Meis1 and Hoxa11 expression domains are overlapping, whereas the Barx1 expression domain resides within the Hoxa11 expression domain. However, once the interzone is formed, the expression domains are refined and the Barx1 expression domain becomes congruent with the border of these two putative segment markers.Publication Proximo-distal positional information encoded by an Fgf-regulated gradient of homeodomain transcription factors in the vertebrate limb.(American Association for the Advancement of Science (AAAS), 2020-06) Delgado, Irene; López-Delgado, Alejandra C; Roselló-Díez, Alberto; Giovinazzo, Giovanna; Cadenas, Vanessa; Fernandez-de-Manuel, Laura; Sanchez-Cabo, Fatima; Anderson, Matthew J; Lewandoski, Mark; Torres, Miguel; Ministerio de Ciencia, Innovación y Universidades (España); Instituto de Salud Carlos III; Comunidad de Madrid (España); Fundación ProCNICThe positional information theory proposes that a coordinate system provides information to embryonic cells about their position and orientation along a patterning axis. Cells interpret this information to produce the appropriate pattern. During development, morphogens and interpreter transcription factors provide this information. We report a gradient of Meis homeodomain transcription factors along the mouse limb bud proximo-distal (PD) axis antiparallel to and shaped by the inhibitory action of distal fibroblast growth factor (FGF). Elimination of Meis results in premature limb distalization and HoxA expression, proximalization of PD segmental borders, and phocomelia. Our results show that Meis transcription factors interpret FGF signaling to convey positional information along the limb bud PD axis. These findings establish a new model for the generation of PD identities in the vertebrate limb and provide a molecular basis for the interpretation of FGF signal gradients during axial patterning.