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Stage specific requirement of Gfr?1 in the ureteric epithelium during kidney development.

ABSTRACT: Glial cell line-derived neurotrophic factor (GDNF) binds a coreceptor GDNF family receptor ?1 (GFR?1) and forms a signaling complex with the receptor tyrosine kinase RET. GDNF-GFR?1-RET signaling activates cellular pathways that are required for normal induction of the ureteric bud (UB) from the Wolffian duct (WD). Failure of UB formation results in bilateral renal agenesis and perinatal lethality. Gfr?1 is expressed in both the epithelial and mesenchymal compartments of the developing kidney while Ret expression is specific to the epithelium. The biological importance of Gfr?1's wider tissue expression and its role in later kidney development are unclear. We discovered that conditional loss of Gfr?1 in the WD epithelium prior to UB branching is sufficient to cause renal agenesis. This finding indicates that Gfr?1 expressed in the nonepithelial structures cannot compensate for this loss. To determine Gfr?1's role in branching morphogenesis after UB induction we used an inducible Gfr?1-specific Cre-deletor strain and deleted Gfr?1 from the majority of UB tip cells post UB induction in vivo and in explant kidney cultures. We report that Gfr?1 excision from the epithelia compartment after UB induction caused a modest reduction in branching morphogenesis. The loss of Gfr?1 from UB-tip cells resulted in reduced cell proliferation and decreased activated ERK (pERK). Further, cells without Gfr?1 expression are able to populate the branching UB tips. These findings delineate previously unclear biological roles of Gfr?1 in the urinary tract and demonstrate its cell-type and stage-specific requirements in kidney development.

SUBMITTER: Keefe Davis T

PROVIDER: S-EPMC3722262 | biostudies-literature | 2013 Sep-Oct

REPOSITORIES: biostudies-literature

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Stage specific requirement of Gfrα1 in the ureteric epithelium during kidney development.

Keefe Davis T T Hoshi Masato M Jain Sanjay S

Mechanisms of development 20130328 9-10

Glial cell line-derived neurotrophic factor (GDNF) binds a coreceptor GDNF family receptor α1 (GFRα1) and forms a signaling complex with the receptor tyrosine kinase RET. GDNF-GFRα1-RET signaling activates cellular pathways that are required for normal induction of the ureteric bud (UB) from the Wolffian duct (WD). Failure of UB formation results in bilateral renal agenesis and perinatal lethality. Gfrα1 is expressed in both the epithelial and mesenchymal compartments of the developing kidney wh ...[more]

PMID: 23542432

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Project description:BACKGROUND: Aedes aegypti is the most important global vector of dengue virus infection in humans. Availability of the draft genome sequence of this mosquito provides unique opportunities to study different aspects of its biology, including identification of genes and pathways relevant to the developmental processes associated with transition across individual life stages. However, detailed knowledge of gene expression patterns pertaining to developmental stages of A. aegypti is largely lacking. RESULTS: We performed custom cDNA microarray analyses to examine the expression patterns among six developmental stages: early larvae, late larvae, early pupae, late pupae, and adult male and female mosquitoes. Results revealed 1,551 differentially expressed transcripts (DETs) showing significant differences in levels of expression between these life stages. The data suggests that most of the differential expression occurs in a stage specific manner in A. aegypti. Based on hierarchical clustering of expression levels, correlated expression patterns of DETs were also observed among developmental stages. Weighted gene correlation network analysis revealed modular patterns of expression among the DETs. We observed that hydrolase activity, membrane, integral to membrane, DNA binding, translation, ribosome, nucleoside-triphosphatase activity, structural constituent of ribosome, ribonucleoprotein complex and receptor activity were among the top ten ranked GO (Gene Ontology) terms associated with DETs. Significant associations of DETs were also observed with specific KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway modules. Finally, comparisons with the previously reported developmental transcriptome of the malaria vector, Anopheles gambiae, indicated that gene expression patterns during developmental processes reflect both species-specific as well as common components of the two mosquito species. CONCLUSIONS: Our study shows that genes involved in the developmental life cycle of A. aegypti are expressed in a highly stage-specific manner. This suggests that transcriptional events associated with transition through larval, pupal and adult stages are largely discrete.

Dataset Information

Stage specific requirement of Gfr?1 in the ureteric epithelium during kidney development.

Publications

Stage specific requirement of Gfrα1 in the ureteric epithelium during kidney development.

Similar Datasets

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