Camilla Bosone, Davide Castaldi, Thomas Rainer Burkard, Segundo Jose Guzman, Tom Wyatt, Cristina Cheroni, Nicolò Caporale, Sunanjay Bajaj, Joshua Adam Bagley, Chong Li, Benoit Sorre, Carlo Emanuele Villa, Giuseppe Testa, Veronica Krenn, Jürgen Arthur Knoblich
{"title":"极化的 FGF8 信号源可确定大脑皮层集合体空间定向细胞群的额颞叶特征","authors":"Camilla Bosone, Davide Castaldi, Thomas Rainer Burkard, Segundo Jose Guzman, Tom Wyatt, Cristina Cheroni, Nicolò Caporale, Sunanjay Bajaj, Joshua Adam Bagley, Chong Li, Benoit Sorre, Carlo Emanuele Villa, Giuseppe Testa, Veronica Krenn, Jürgen Arthur Knoblich","doi":"10.1038/s41592-024-02412-5","DOIUrl":null,"url":null,"abstract":"Organoids generating major cortical cell types in distinct compartments are used to study cortical development, evolution and disorders. However, the lack of morphogen gradients imparting cortical positional information and topography in current systems hinders the investigation of complex phenotypes. Here, we engineer human cortical assembloids by fusing an organizer-like structure expressing fibroblast growth factor 8 (FGF8) with an elongated organoid to enable the controlled modulation of FGF8 signaling along the longitudinal organoid axis. These polarized cortical assembloids mount a position-dependent transcriptional program that in part matches the in vivo rostrocaudal gene expression patterns and that is lost upon mutation in the FGFR3 gene associated with temporal lobe malformations and intellectual disability. By producing spatially oriented cell populations with signatures related to frontal and temporal area identity within individual assembloids, this model recapitulates in part the early transcriptional divergence embedded in the protomap and enables the study of cortical area-relevant alterations underlying human disorders. Cortical development is influenced by morphogen gradients. To mimic patterning events during brain development, polarized cortical assembloids are generated with the help of a localized FGF8 source.","PeriodicalId":18981,"journal":{"name":"Nature Methods","volume":"21 11","pages":"2147-2159"},"PeriodicalIF":36.1000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41592-024-02412-5.pdf","citationCount":"0","resultStr":"{\"title\":\"A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids\",\"authors\":\"Camilla Bosone, Davide Castaldi, Thomas Rainer Burkard, Segundo Jose Guzman, Tom Wyatt, Cristina Cheroni, Nicolò Caporale, Sunanjay Bajaj, Joshua Adam Bagley, Chong Li, Benoit Sorre, Carlo Emanuele Villa, Giuseppe Testa, Veronica Krenn, Jürgen Arthur Knoblich\",\"doi\":\"10.1038/s41592-024-02412-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Organoids generating major cortical cell types in distinct compartments are used to study cortical development, evolution and disorders. However, the lack of morphogen gradients imparting cortical positional information and topography in current systems hinders the investigation of complex phenotypes. Here, we engineer human cortical assembloids by fusing an organizer-like structure expressing fibroblast growth factor 8 (FGF8) with an elongated organoid to enable the controlled modulation of FGF8 signaling along the longitudinal organoid axis. These polarized cortical assembloids mount a position-dependent transcriptional program that in part matches the in vivo rostrocaudal gene expression patterns and that is lost upon mutation in the FGFR3 gene associated with temporal lobe malformations and intellectual disability. By producing spatially oriented cell populations with signatures related to frontal and temporal area identity within individual assembloids, this model recapitulates in part the early transcriptional divergence embedded in the protomap and enables the study of cortical area-relevant alterations underlying human disorders. Cortical development is influenced by morphogen gradients. 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A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids
Organoids generating major cortical cell types in distinct compartments are used to study cortical development, evolution and disorders. However, the lack of morphogen gradients imparting cortical positional information and topography in current systems hinders the investigation of complex phenotypes. Here, we engineer human cortical assembloids by fusing an organizer-like structure expressing fibroblast growth factor 8 (FGF8) with an elongated organoid to enable the controlled modulation of FGF8 signaling along the longitudinal organoid axis. These polarized cortical assembloids mount a position-dependent transcriptional program that in part matches the in vivo rostrocaudal gene expression patterns and that is lost upon mutation in the FGFR3 gene associated with temporal lobe malformations and intellectual disability. By producing spatially oriented cell populations with signatures related to frontal and temporal area identity within individual assembloids, this model recapitulates in part the early transcriptional divergence embedded in the protomap and enables the study of cortical area-relevant alterations underlying human disorders. Cortical development is influenced by morphogen gradients. To mimic patterning events during brain development, polarized cortical assembloids are generated with the help of a localized FGF8 source.
期刊介绍:
Nature Methods is a monthly journal that focuses on publishing innovative methods and substantial enhancements to fundamental life sciences research techniques. Geared towards a diverse, interdisciplinary readership of researchers in academia and industry engaged in laboratory work, the journal offers new tools for research and emphasizes the immediate practical significance of the featured work. It publishes primary research papers and reviews recent technical and methodological advancements, with a particular interest in primary methods papers relevant to the biological and biomedical sciences. This includes methods rooted in chemistry with practical applications for studying biological problems.