RGD Reference Report - A role for Timeless in epithelial morphogenesis during kidney development. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

A role for Timeless in epithelial morphogenesis during kidney development.

Authors: Li, Z  Stuart, RO  Qiao, J  Pavlova, A  Bush, KT  Pohl, M  Sakurai, H  Nigam, SK 
Citation: Li Z, etal., Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10038-43.
RGD ID: 2308864
Pubmed: PMID:10963667   (View Abstract at PubMed)
PMCID: PMC27664   (View Article at PubMed Central)

Central to the process of epithelial organogenesis is branching morphogenesis into tubules and ducts. In the kidney, this can be modeled by a very simple system consisting of isolated ureteric bud (UB) cells, which undergo branching morphogenesis in response to soluble factors present in the conditioned medium of a metanephric mesenchyme cell line. By employing a targeted screen to identify transcription factors involved early in the morphogenetic program leading to UB branching, we identified the mammalian ortholog of Timeless (mTim) as a potential immediate early gene (IEG) important in this process. In the embryo, mTim was found to be expressed in patterns very suggestive of a role in epithelial organogenesis with high levels of expression in the developing lung, liver, and kidney, as well as neuroepithelium. In the embryonic kidney, the expression of mTim was maximal in regions of active UB branching, and a shift from the large isoform of mTim to a smaller isoform occurred as the kidney developed. Selective down-regulation of mTim resulted in profound inhibition of embryonic kidney growth and UB morphogenesis in organ culture. A direct effect on the branching UB was supported by the observation that down-regulation of mTim in the isolated UB (cultured in the absence of mesenchyme) resulted in marked inhibition of morphogenesis, suggesting a key role for Tim in the epithelial cell morphogenetic pathway leading to the formation of branching tubules.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TimelessRatbranching involved in ureteric bud morphogenesis acts_upstream_of_or_withinIMP PMID:10963667MGI 
TimelessRatbranching involved in ureteric bud morphogenesis  IMP  RGD 
TimelessRatkidney development  IMP  RGD 
TimelessRatmorphogenesis of an epithelium involved_inIEP PMID:10963667UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Timeless  (timeless circadian regulator)


Additional Information