Dissecting spatio-temporal protein networks driving human heart development and related disorders
Aberrant organ development is associated with a wide spectrum of disorders, from schizophrenia to congenital heart disease, but systems-level insight into the underlying processes is very limited. Using heart morphogenesis as general model for dissecting the functional architecture of organ developm...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group / European Molecular Biology Organization (EMBO)
2011
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| Online Access: | http://hdl.handle.net/1721.1/61761 |
| _version_ | 1811095244187369472 |
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| author | Lage, Kasper Møllgård, Kjeld Greenway, Steven Wakimoto, Hiroko Gorham, Joshua M. Workman, Christopher T. Bendsen, Eske Hansen, Niclas T. Rigina, Olga Roque, Francisco S. Wiese, Cornelia Christoffels, Vincent M. Roberts, Amy E. Smoot, Leslie B. Pu, William T. Donahoe, Patricia Tommerup, Niels Brunak, Søren Seidman, Christine E. Seidman, Jonathan G. Larsen, Lars A. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Lage, Kasper Møllgård, Kjeld Greenway, Steven Wakimoto, Hiroko Gorham, Joshua M. Workman, Christopher T. Bendsen, Eske Hansen, Niclas T. Rigina, Olga Roque, Francisco S. Wiese, Cornelia Christoffels, Vincent M. Roberts, Amy E. Smoot, Leslie B. Pu, William T. Donahoe, Patricia Tommerup, Niels Brunak, Søren Seidman, Christine E. Seidman, Jonathan G. Larsen, Lars A. |
| author_sort | Lage, Kasper |
| collection | MIT |
| description | Aberrant organ development is associated with a wide spectrum of disorders, from schizophrenia to congenital heart disease, but systems-level insight into the underlying processes is very limited. Using heart morphogenesis as general model for dissecting the functional architecture of organ development, we combined detailed phenotype information from deleterious mutations in 255 genes with high-confidence experimental interactome data, and coupled the results to thorough experimental validation. Hereby, we made the first systematic analysis of spatio-temporal protein networks driving many stages of a developing organ identifying several novel signaling modules. Our results show that organ development relies on surprisingly few, extensively recycled, protein modules that integrate into complex higher-order networks. This design allows the formation of a complicated organ using simple building blocks, and suggests how mutations in the same genes can lead to diverse phenotypes. We observe a striking temporal correlation between organ complexity and the number of discrete functional modules coordinating morphogenesis. Our analysis elucidates the organization and composition of spatio-temporal protein networks that drive the formation of organs, which in the future may lay the foundation of novel approaches in treatments, diagnostics, and regenerative medicine. |
| first_indexed | 2024-09-23T16:13:54Z |
| format | Article |
| id | mit-1721.1/61761 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:13:54Z |
| publishDate | 2011 |
| publisher | Nature Publishing Group / European Molecular Biology Organization (EMBO) |
| record_format | dspace |
| spelling | mit-1721.1/617612022-10-02T07:08:10Z Dissecting spatio-temporal protein networks driving human heart development and related disorders Lage, Kasper Møllgård, Kjeld Greenway, Steven Wakimoto, Hiroko Gorham, Joshua M. Workman, Christopher T. Bendsen, Eske Hansen, Niclas T. Rigina, Olga Roque, Francisco S. Wiese, Cornelia Christoffels, Vincent M. Roberts, Amy E. Smoot, Leslie B. Pu, William T. Donahoe, Patricia Tommerup, Niels Brunak, Søren Seidman, Christine E. Seidman, Jonathan G. Larsen, Lars A. Harvard University--MIT Division of Health Sciences and Technology Donahoe, Patricia Donahoe, Patricia Aberrant organ development is associated with a wide spectrum of disorders, from schizophrenia to congenital heart disease, but systems-level insight into the underlying processes is very limited. Using heart morphogenesis as general model for dissecting the functional architecture of organ development, we combined detailed phenotype information from deleterious mutations in 255 genes with high-confidence experimental interactome data, and coupled the results to thorough experimental validation. Hereby, we made the first systematic analysis of spatio-temporal protein networks driving many stages of a developing organ identifying several novel signaling modules. Our results show that organ development relies on surprisingly few, extensively recycled, protein modules that integrate into complex higher-order networks. This design allows the formation of a complicated organ using simple building blocks, and suggests how mutations in the same genes can lead to diverse phenotypes. We observe a striking temporal correlation between organ complexity and the number of discrete functional modules coordinating morphogenesis. Our analysis elucidates the organization and composition of spatio-temporal protein networks that drive the formation of organs, which in the future may lay the foundation of novel approaches in treatments, diagnostics, and regenerative medicine. Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (RO1 grant HD055150-03) 2011-03-22T21:38:18Z 2011-03-22T21:38:18Z 2010-06 2009-09 Article http://purl.org/eprint/type/JournalArticle 1744-4292 http://hdl.handle.net/1721.1/61761 Lage, Kasper et al. “Dissecting spatio-temporal protein networks driving human heart development and related disorders.” Mol Syst Biol 6 (2010): n. pag. © 2011 Nature Publishing Group en_US http://dx.doi.org/10.1038/msb.2010.36 Molecular Systems Biology Creative Commons Attribution-Non-Commercial-Share Alike 3.0 http://creativecommons.org/licenses/by/3.0 application/pdf Nature Publishing Group / European Molecular Biology Organization (EMBO) Molecular Systems Biology |
| spellingShingle | Lage, Kasper Møllgård, Kjeld Greenway, Steven Wakimoto, Hiroko Gorham, Joshua M. Workman, Christopher T. Bendsen, Eske Hansen, Niclas T. Rigina, Olga Roque, Francisco S. Wiese, Cornelia Christoffels, Vincent M. Roberts, Amy E. Smoot, Leslie B. Pu, William T. Donahoe, Patricia Tommerup, Niels Brunak, Søren Seidman, Christine E. Seidman, Jonathan G. Larsen, Lars A. Dissecting spatio-temporal protein networks driving human heart development and related disorders |
| title | Dissecting spatio-temporal protein networks driving human heart development and related disorders |
| title_full | Dissecting spatio-temporal protein networks driving human heart development and related disorders |
| title_fullStr | Dissecting spatio-temporal protein networks driving human heart development and related disorders |
| title_full_unstemmed | Dissecting spatio-temporal protein networks driving human heart development and related disorders |
| title_short | Dissecting spatio-temporal protein networks driving human heart development and related disorders |
| title_sort | dissecting spatio temporal protein networks driving human heart development and related disorders |
| url | http://hdl.handle.net/1721.1/61761 |
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