{"id":20260,"date":"2026-04-08T11:28:10","date_gmt":"2026-04-08T10:28:10","guid":{"rendered":"https:\/\/cabd.es\/investigation\/departments\/regulacion-genica-y-morfogenesis\/dra-maria-almuedo-castillo\/"},"modified":"2026-11-03T11:43:35","modified_gmt":"2026-11-03T10:43:35","slug":"dra-maria-almuedo-castillo","status":"publish","type":"page","link":"https:\/\/cabd.es\/en\/investigation\/departments\/multicelular-dynamics\/dra-maria-almuedo-castillo\/","title":{"rendered":"Dra Mar\u00eda Almuedo-Castillo"},"content":{"rendered":"

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Multicellular Dynamics<\/p>\n

Mechanosensitive cellular apparatus and gene regulation during early embryonic development<\/h1>\n

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Dra Mar\u00eda Almuedo-Castillo<\/h4>\n

Principal Investigator<\/p>\n

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Summary<\/h2>\n
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Cells are able to sense mechanical cues from their environment and respond by activating distinct genetic and biochemical signalling cascades that influence cell differentiation and function. This connection, which remains poorly explored, is likely to play a critical role during embryonic development and organ formation, as embryonic cells are highly dynamic in nature. They are constantly moving, undergoing profound changes in shape, and interacting with diverse environments that exert different mechanical forces upon them. However, we still do not understand how these forces are integrated at the genetic and molecular level, nor what type of cellular memory is used to faithfully propagate mechanical or geometrical changes over time.

The overarching goal of the laboratory is therefore to elucidate how external mechanical forces are translated into distinct cellular and nuclear conformational states, and consequently into gene regulatory signals, during early vertebrate embryonic development.<\/strong><\/p>\n

YAP is one of the best-characterised mechanosensitive proteins, acting as a sensor that transduces mechanical signals into biochemical processes and changes in the transcriptional state of the cell.\u00a0Our objective is to use YAP as a reference indicator to identify additional mechanosensitive proteins, which together would constitute a cellular connectome\u00a0responsible for transmitting environmental information to the cell.<\/strong>\u00a0This approach will also enable us to investigate how nuclear geometry and substrate-derived mechanical forces impact the global epigenome, which we will define as a set of mechanosensitive gene regulatory regions (mGRRs).<\/strong>\u00a0In parallel, we will identify\u00a0changes in the cellular mechanosensing apparatus using high-resolution microscopy techniques and link these structural alterations to the differential usage of mGRRs under a range of mechanical perturbations.<\/strong><\/p>\n

We will subsequently exploit these mGRRs to study mechanosensitive processes during embryonic development, including the emergence of early \u201cmechanical boundaries\u201d and morphogenetic events known to depend on highly specific cellular geometries, such as collective cell migration or epiboly during gastrulation and optic cup formation. Finally, we will integrate all this information to compare development in vivo (embryos) and in vitro\u00a0(organoids), and to determine the extent to which gene regulation\u2014and in particular mechanosensitive regulation\u2014is conserved in organoids. This will allow us to identify the biological substrates that most faithfully recapitulate the in vivo organism, not only at the morphological level, but also at the epigenetic level.<\/p>\n<\/div>\n

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Five relevant publications<\/h2>\n
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  • Sousa-Ortega A*, V\u00e1zquez-Mar\u00edn J*, Sanabria-Reinoso E, Polvillo R, Campoy-Lopez A, Buono L, Loosli F, Almuedo-Castillo M#, Mart\u00ednez-Morales JR# (2023). A Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly.\u00a0Nat Commun\u00a014:2804. *equally contributing,\u00a0 #corresponding authors.<\/li>\n
  • Buono L, Corbacho J, Naranjo S, Almuedo-Castillo M, Moreno-Marmol T, de la Cerda B, Sanabria-Reinoso E, Polvillo R, D\u00edaz-Corrales FJ, Bogdanovic O, Bovolenta P, Mart\u00ednez-Morales JR (2021). Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish. Nat Commun. 12:3866.<\/li>\n
  • Cadozo M*, Almuedo-Castillo M* and Bovolenta P. (2020) Patterning the Vertebrate Retina with Morphogenetic Signaling Pathways. Neuroscientist. 26:185.<\/li>\n
  • V\u00e1zquez-Mar\u00edn J, Guti\u00e9rrez-Triana JA, Almuedo-Castillo M, Buono L, G\u00f3mez-Skarmeta JL, Mateo JL, Wittbrodt J, Mart\u00ednez-Morales JR. (2019).\u00a0yap1b, a divergent Yap\/Taz family member, cooperates with\u00a0yap1\u00a0in survival and morphogenesis via common transcriptional targets.\u00a0Development. 146:dev173286.<\/li>\n
  • Almuedo-Castillo M, Bl\u00e4\u00dfle A, M\u00f6rsdorf D, Marcon L, Rogers KW, Soh GH, Schier AF, M\u00fcller P. (2018) Scale-invariant patterning by size-dependent inhibition of Nodal signaling. Nature Cell Biology. 20:1032.<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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    Lab members & collaborators<\/h2>\n
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    Lab members<\/h3>\n

    Group Leader:\u00a0<\/h4>\n

    Mar\u00eda Almuedo-Castillo.<\/strong><\/p>\n

    Lab Manager:<\/h4>\n

    <\/strong>Estefan\u00eda Sanabria-Reinoso.
    <\/strong>Bioinformatician:Jes\u00fas Garc\u00eda-Junco Alcala.<\/strong><\/p>\n

    PhD. Student<\/h4>\n

    <\/strong>(co-supervised with O Bogdanovic, CABD): Juan Aperador Redondo (FPI).
    PhD. Student:\u00a0<\/strong>Andrea Mart\u00ednez Vara (FPI).
    PhD. Student:\u00a0<\/strong>Giulio Storari (MSCA).
    PhD. Student:\u00a0<\/strong>Nicholas de Jager (HFSP).<\/p>\n

    FORMER Lab members<\/h4>\n

    PhD: Ana Sousa Ortega (co-supervised with JR Martinez-Morales, CABD).
    PhD:\u00a0Maria Jos\u00e9 L\u00f3pez Fern\u00e1ndez\u00a0(co-supervised with I Maeso, UB).
    Master: Jorge Mason.
    Undergraduate:\u00a0Daniel Segura.<\/p>\n

    COLLABORATORS<\/h3>\n

    Ozren Bogdanovic (CABD, CSIC)
    Juan Ram\u00f3n Martinez-Morales (CABD, CSIC)
    Nacho Maeso (Univeristy of Barcelona)
    Alessandro Mongera (Univeristy College of London)
    Mattia Serra (University of Oregon)
    Alexander Blaessle (Novartis Basel)<\/p>\n

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