REGULATION OF PODOCYTE DEVELOPMENT INXENOPUS

Document Type

Presentation

Start Date

22-10-2010 10:45 AM

End Date

22-10-2010 12:00 PM

Description

Podocytes are highly specified cells present in the glomus/glomerulus of vertebrate kidney. They are part of a size-exclusion barrier and crucial for the kidney function. Defects in podocyte always cause for the loss of kidney function. Many transcription factors including wt1, foxc2, hey1, tcf21, lmx1 b and mafb have been demonstrated to function in podocyte development. However, the studies so far were mostly based on the single gene knockouts in the mouse and the precise spatial-temporal interactions of these transcription factors to drive the podocyte development are still poorly understood. To address this question, we used the Xenopus pronephrons as a paradigm. We first demonstrated the spatial-temporal expression of the transcription factors using whole mount in situ hybridization. Subsequently, all six transcription factors were eliminated either alone or in combination using antisense morpholino oligomers. Podocyte development was assayed using morphology, histology and gene expression analysis. The data established a gene regulatory network for podocyte development based on six transcription factors and four terminal differentiation markers including nphs1, kirre/, ptpru and nphs2. Interestingly, only the selective knockdown of WT1 and Foxc2 was sufficient to turn off the expression of all terminal differentiation markers and prevent the formation of functional podocytes. Conversely, overexpression of WT1 and Foxc2 by injection of synthetical mRNA could upregulate podocytes gene expression in the glomus but Notch signaling was required for ectopic expression of podocyte gene.

In summary, our study provided a novel view about podocyte development emphasizing the interaction between transcription factors and signaling pathway.

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Oct 22nd, 10:45 AM Oct 22nd, 12:00 PM

REGULATION OF PODOCYTE DEVELOPMENT INXENOPUS

Podocytes are highly specified cells present in the glomus/glomerulus of vertebrate kidney. They are part of a size-exclusion barrier and crucial for the kidney function. Defects in podocyte always cause for the loss of kidney function. Many transcription factors including wt1, foxc2, hey1, tcf21, lmx1 b and mafb have been demonstrated to function in podocyte development. However, the studies so far were mostly based on the single gene knockouts in the mouse and the precise spatial-temporal interactions of these transcription factors to drive the podocyte development are still poorly understood. To address this question, we used the Xenopus pronephrons as a paradigm. We first demonstrated the spatial-temporal expression of the transcription factors using whole mount in situ hybridization. Subsequently, all six transcription factors were eliminated either alone or in combination using antisense morpholino oligomers. Podocyte development was assayed using morphology, histology and gene expression analysis. The data established a gene regulatory network for podocyte development based on six transcription factors and four terminal differentiation markers including nphs1, kirre/, ptpru and nphs2. Interestingly, only the selective knockdown of WT1 and Foxc2 was sufficient to turn off the expression of all terminal differentiation markers and prevent the formation of functional podocytes. Conversely, overexpression of WT1 and Foxc2 by injection of synthetical mRNA could upregulate podocytes gene expression in the glomus but Notch signaling was required for ectopic expression of podocyte gene.

In summary, our study provided a novel view about podocyte development emphasizing the interaction between transcription factors and signaling pathway.