Dataset Information

Dissecting spatio-temporal protein networks driving human heart development and related disorders.

ABSTRACT: 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.

SUBMITTER: Lage K

PROVIDER: S-EPMC2913399 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Dissecting spatio-temporal protein networks driving human heart development and related disorders.

Lage Kasper K Møllgård Kjeld K Greenway Steven S Wakimoto Hiroko H Gorham Joshua M JM Workman Christopher T CT Bendsen Eske E Hansen Niclas T NT Rigina Olga O Roque Francisco S FS Wiese Cornelia C Christoffels Vincent M VM Roberts Amy E AE Smoot Leslie B LB Pu William T WT Donahoe Patricia K PK Tommerup Niels N Brunak Søren S Seidman Christine E CE Seidman Jonathan G JG Larsen Lars A LA

Molecular systems biology 20100601

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. ...[more]

PMID: 20571530

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Project description:Despite its high ecological importance, the commensal interactions at community level are poorly studied. In tropical dry forests (TDF) there is a great diversity of species adapted to the high seasonality that characterizes them; however, little is known regarding how the spatial and temporal availability of resources generates changes in the pattern of commensal interactions. We experimentally studied changes in the diversity, composition, and pattern of interactions in spatio-temporal associations between the saproxylophagous beetles and their host trees in a TDF in Morelos, Mexico. A total of 65 host tree species were selected, from which 16 wood sections were obtained per species. These sections were exposed in the field to allow oviposition by the cerambycids under four different (spatio-temporal) treatments. We analyzed the network structure and generated indices at species level (i.e., specialization, species strength, and effective partners) and those related to physical characteristics of the wood (hardness and degradation rate) and the cerambycids (body size). In total, 1,323 individuals of 57 species of cerambycids emerged. Our results showed that, independently of the space and time, the network presented a nested and modular structure, with a high specialization degree and a high turnover of cerambycid species and their interactions. In general, we found that the cerambycids are mostly associated with softwood species with a lower decomposition rate of wood, as well as with the most abundant host species. The commensalistic interactions between the cerambycids and their host trees are highly specialized but are not spatio-temporally static. The high turnover in the interactions is caused by the emergence patterns of cerambycids, which seem to restrict their use to certain species. The knowledge of the spatio-temporal variation in Cerambycidae-host tree interactions allows us to predict how environmental and structural changes in the habitat can modify the species ensemble, and therefore its interactions.

Dataset Information

Dissecting spatio-temporal protein networks driving human heart development and related disorders.

Publications

Dissecting spatio-temporal protein networks driving human heart development and related disorders.

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