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Analysis of metagene portraits reveals distinct transitions during kidney organogenesis.

ABSTRACT: Organogenesis is a multistage process, but it has been difficult, by conventional analysis, to separate stages and identify points of transition in developmentally complex organs or define genetic pathways that regulate pattern formation. We performed a detailed time-series examination of global gene expression during kidney development and then represented the resulting data as self-organizing maps (SOMs), which reduced more than 30,000 genes to 650 metagenes. Further clustering of these maps identified potential stages of development and suggested points of stability and transition during kidney organogenesis that are not obvious from either standard morphological analyses or conventional microarray clustering algorithms. We also performed entropy calculations of SOMs generated for each day of development and found correlations with morphometric parameters and expression of candidate genes that may help in orchestrating the transitions between stages of kidney development, as well as macro- and micropatterning of the organ.

SUBMITTER: Tsigelny IF

PROVIDER: S-EPMC3016920 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Analysis of metagene portraits reveals distinct transitions during kidney organogenesis.

Tsigelny Igor F IF Kouznetsova Valentina L VL Sweeney Derina E DE Wu Wei W Bush Kevin T KT Nigam Sanjay K SK

Science signaling 20081209 49

Organogenesis is a multistage process, but it has been difficult, by conventional analysis, to separate stages and identify points of transition in developmentally complex organs or define genetic pathways that regulate pattern formation. We performed a detailed time-series examination of global gene expression during kidney development and then represented the resulting data as self-organizing maps (SOMs), which reduced more than 30,000 genes to 650 metagenes. Further clustering of these maps i ...[more]

PMID: 19066399

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Project description:Bone morphogenetic proteins (BMPs) regulate essential processes during organogenesis, and a functional understanding of these secreted proteins depends on identification of their target cells. In this study, we generate a transgenic reporter for organogenesis studies that we use to define BMP pathway activation in the developing kidney.Mouse strains reporting on BMP pathway activation were generated by transgenically expressing beta-galactosidase under the control of BMP responsive elements from Id1. Reporter expression corresponds well with immunoassays for pathway activation in all organs studied, validating the model. Using these reporters we have generated a detailed map of cellular targets of BMP signaling in the developing kidney. We find that SMAD dependent BMP signaling is active in collecting duct trunks, but not tips. Furthermore, glomerular endothelial cells, and proximal nephron tubules from the renal vesicle stage onward show pathway activation. Surprisingly, little activation is detected in the nephrogenic zone of the kidney, and in organ culture BMP treatment fails to activate SMAD dependent BMP signaling in nephron progenitor cells. In contrast, signaling is efficiently induced in collecting duct tips.Transgenic reporters driven by control elements from BMP responsive genes such as Id1 offer significant advantages in sensitivity and consistency over immunostaining for studies of BMP pathway activation. They also provide opportunities for analysis of BMP signaling in organ and primary cell cultures subjected to experimental manipulation. Using such a reporter, we made the surprising finding that SMAD dependent BMP signaling is inactive in nephron progenitors, and that these cells are refractory to activation by applied growth factors. Furthermore, we find that the BMP pathway is not normally active in collecting duct tips, but that it can be ectopically activated by BMP treatment, offering a possible explanation for the inhibitory effects of BMP treatment on collecting duct growth and branching.

Dataset Information

Analysis of metagene portraits reveals distinct transitions during kidney organogenesis.

Publications

Analysis of metagene portraits reveals distinct transitions during kidney organogenesis.

Similar Datasets

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