Linked Life Data

15342483

Source:http://linkedlifedata.com/resource/pubmed/id/15342483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2004-9-2
pubmed:abstractText
The TGFbeta superfamily plays diverse and essential roles in kidney development. Gdf11 and Bmp4 are essential for outgrowth and positioning of the ureteric bud, the inducer of metanephric mesenchyme. During nephrogenesis, Bmp7 is required for renewal of the mesenchyme progenitor population. Additionally, in vitro studies demonstrate inhibitory effects of BMPs and TGFbetas on collecting duct branching and growth. Here, we explore the predicted models of TGFbeta superfamily function by cell-specific inactivation of Smad4, a key mediator of TGFbeta signaling. Using a HoxB7cre transgene expressed in ureteric bud and collecting duct, we find that development of the collecting duct is Smad4 independent. By contrast, removal of Smad4 in nephrogenic mesenchyme using the Bmp7(cre/+) allele leads to disorganization of the nephrogenic mesenchyme and impairment of mesenchyme induction. Smad4-deficient metanephric mesenchyme does not display defects in inducibility in LiCl or spinal cord induction assays. However, in situ hybridization and lineage analysis of Smad4 null mesenchyme cells at E11.5 show that the nephrogenic mesenchyme does not aggregate tightly around the ureteric bud tips, but remains loosely associated, embedded within a population of cells expressing markers of both nephrogenic mesenchyme and peripheral stroma. We conclude that the failure of recruitment of nephrogenic mesenchyme leaves a primitive population of mesenchyme at the periphery of the kidney. This population is gradually depleted, and by E16.5 the periphery is composed of cells of stromal phenotype. This study uncovers a novel role for TGFbeta superfamily signaling in the recruitment and/or organization of the nephrogenic mesenchyme at early time-points of kidney development. Additionally, we present conclusive genetic lineage mapping of the collecting duct and nephrogenic mesenchyme.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4593-605
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15342483-Animals, pubmed-meshheading:15342483-Bone Morphogenetic Protein 7, pubmed-meshheading:15342483-Bone Morphogenetic Proteins, pubmed-meshheading:15342483-Cell Division, pubmed-meshheading:15342483-Cell Lineage, pubmed-meshheading:15342483-DNA-Binding Proteins, pubmed-meshheading:15342483-Gene Deletion, pubmed-meshheading:15342483-Homeodomain Proteins, pubmed-meshheading:15342483-Kidney, pubmed-meshheading:15342483-Mesoderm, pubmed-meshheading:15342483-Mice, pubmed-meshheading:15342483-Mice, Transgenic, pubmed-meshheading:15342483-Morphogenesis, pubmed-meshheading:15342483-Multigene Family, pubmed-meshheading:15342483-Nephrosis, pubmed-meshheading:15342483-Signal Transduction, pubmed-meshheading:15342483-Smad4 Protein, pubmed-meshheading:15342483-Stem Cells, pubmed-meshheading:15342483-Trans-Activators, pubmed-meshheading:15342483-Transforming Growth Factor beta
pubmed:year
2004
pubmed:articleTitle
TGFbeta superfamily signals are required for morphogenesis of the kidney mesenchyme progenitor population.
pubmed:affiliation
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't