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Título: | Deregulation of the epithelial-to-mesenchymal transition process underlies Zic2-linked holoprosencephaly |
Autor: | Giner de Gracia, Aida; Morenilla-Palao, Cruz CSIC ORCID; López-Cascales, María Teresa CSIC ORCID; Muça, Gerald CSIC; Barco, Ángel CSIC ORCID ; Herrera, Eloisa CSIC ORCID | Fecha de publicación: | 2021 | Citación: | 19th Meeting Spanish Society of Neuroscience (2021) | Resumen: | Holoprosencephaly (HPE) is a congenital brain malformation resulting from incomplete separation of the two hemispheres. Mutations in the Zic2 gene cause holoprosencephaly type 5, but the mechanisms that translate Zic2 mutations into this devastating pathology remain unclear. Here, we report that Zic2 is expressed in a few epiblast cells during gastrulation to become transiently upregulated in the primitive streak. Later, during neurulation, Zic2 is re-expressed in neural crest cells and downregulated as they delaminate from the neural tube. In combination with transcriptomic data from mutant embryos, chromatin occupancy profiles in gastrula and neural crest cells reveal that Zic2 regulates a large number of genes associated with the Wnt, cadherin and TGF-β pathways. In proliferating cells exposed to Wnt, Zic2 prevents the translocation of β- catenin to the nucleus, subsequently accumulating in the cytoplasm. This blocks activation of the canonical pathway inducing a non-canonical Wnt response necessary to initiate EMT. Our results elucidate the role of Zic2 in early development and provide an explanation for the wide variety of developmental alterations in HPE5 patients that, unlike other HPE patients, include many other mesoderm-derived defects. Altogether, these analyses identify cell types, signaling cascades, and genomic regions implicated in the etiology of Zic2-linked neurodevelopmental disorders. | Descripción: | Resumen del póster presentado al 19th Meeting Spanish Society of Neuroscience (SENC), celebrado en Lleida del 3 al 5 de noviembre de 2021. | URI: | http://hdl.handle.net/10261/269587 |
Aparece en las colecciones: | (IN) Comunicaciones congresos |
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