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Molecular mechanisms underlying vertebrate kidney organogenesis

English title Molecular mechanisms underlying vertebrate kidney organogenesis
Applicant Brändli André
Number 114102
Funding scheme Project funding (Div. I-III)
Research institution Institut für Pharmazeutische Wissenschaften ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Embryology, Developmental Biology
Start/End 01.12.2006 - 31.01.2009
Approved amount 131'300.00
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Keywords (6)

organogenesis; kidney; patterning; transcription factors; Irx; Sim

Lay Summary (English)

Lead
Lay summary
BackgroundKidney organogenesis is a complex process requiring the generation of nephrons, the functional units of the kidney, from nephrogenic mesenchyme.This process is driven by inductive interactions leading to mesenchyme-to-epithelium transitions and the onset of nephrogenesis.Subsequent maturation is characterized by nephron patterning, establishment of proximal-distal segment identity, tubular and glomerular growth and differentiation, and acquisition of specialized functions. In recent years, we have gained lots of insights into the signals and molecules that control the early stages of nephrogenesis. Little is however known about the processes that underlie regionalization and patterning of the nephron and will give rise to the expression of specialized nephron segment-specific transport proteins.Our laboratory has established the Xenopus pronephric kidney as a simple model organ for functional studies of vertebrate nephrogenesis. We have cloned and characterized on a genome-wide scale Xenopus solute carrier(Slc) genes. Analysis of their expression patterns has revealed a segmental organization of the pronephric nephron, which is largely comparable to its mammalian counterpart. Taken together, we are now in a position to dissect in Xenopus the molecular mechanisms for patterning and cell fate decisions during nephrogenesis.Specific aimsIn the present research project, we postulate key roles for two transcription factor families, Irx and Sim, in the regionalization and patterning of the vertebrate nephron. We have demonstrated to date that members of both gene families are expressed in a regionalized manner in the developing Xenopus nephron. Furthermore, our preliminary studies of Irx gene functions suggest a role in specifying intermediate tubule fate in the pronephric kidney. The specific aims of the project are therefore as follows:- Dissection of Irx and Sim gene functions during pronephric kidney development using loss-of-function approaches in the Xenopus embryo- Assessment whether Irx and Sim genes are sufficient to specify renal cell fates by performing gain-of-function studies in renal cell lines, pronephric organ cultures, and Xenopus embryos- Identification of Irx and Sim target genes by microarray-based gene expression profiling- Engineering of embryonic stem cells towards specific renal cell fates by transcription factor overexpressionImpactWe anticipate that the current studies will provide novel insights into the transcriptional mechanisms that pattern the developing nephron and generate the distinct cell types of the different physiological compartments of the vertebrate kidney. Furthermore, we will explore the possibility of using transcription factors to generate defined renal cell types from embryonic stem cells. Theses studies may become the basis for the development of future cell-based therapies to treat acute and chronic renal disease.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
101964 Molecular mechanisms underlying kidney organogenesis and vascular development of Xenopus 01.10.2003 Project funding (Div. I-III)

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