Dissecting spatio-temporal protein networks driving human heart development and related disorders
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Dissecting spatio-temporal protein networks driving human heart development and related disorders. / Hansen, Kasper Lage; 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 K; Tommerup, Niels; Brunak, Søren; Seidman, Christine E; Seidman, Jonathan G; Larsen, Lars A.
In: Molecular Systems Biology, Vol. 6, 2010, p. 381.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Dissecting spatio-temporal protein networks driving human heart development and related disorders
AU - Hansen, Kasper Lage
AU - Møllgård, Kjeld
AU - Greenway, Steven
AU - Wakimoto, Hiroko
AU - Gorham, Joshua M
AU - Workman, Christopher T
AU - Bendsen, Eske
AU - Hansen, Niclas T
AU - Rigina, Olga
AU - Roque, Francisco S
AU - Wiese, Cornelia
AU - Christoffels, Vincent M
AU - Roberts, Amy E
AU - Smoot, Leslie B
AU - Pu, William T
AU - Donahoe, Patricia K
AU - Tommerup, Niels
AU - Brunak, Søren
AU - Seidman, Christine E
AU - Seidman, Jonathan G
AU - Larsen, Lars A
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1038/msb.2010.36
DO - 10.1038/msb.2010.36
M3 - Journal article
C2 - 20571530
VL - 6
SP - 381
JO - Molecular Systems Biology
JF - Molecular Systems Biology
SN - 1744-4292
ER -
ID: 20853237