Atlas of Gene Expression in the Developing Kidney at Microanatomic Resolution

Division of Developmental Biology, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Developmental Cell (Impact Factor: 9.71). 12/2008; 15(5):781-91. DOI: 10.1016/j.devcel.2008.09.007
Source: PubMed


Kidney development is based on differential cell-type-specific expression of a vast number of genes. While multiple critical genes and pathways have been elucidated, a genome-wide analysis of gene expression within individual cellular and anatomic structures is lacking. Accomplishing this could provide significant new insights into fundamental developmental mechanisms such as mesenchymal-epithelial transition, inductive signaling, branching morphogenesis, and segmentation. We describe here a comprehensive gene expression atlas of the developing mouse kidney based on the isolation of each major compartment by either laser capture microdissection or fluorescence-activated cell sorting, followed by microarray profiling. The resulting data agree with known expression patterns and additional in situ hybridizations. This kidney atlas allows a comprehensive analysis of the progression of gene expression states during nephrogenesis, as well as discovery of potential growth factor-receptor interactions. In addition, the results provide deeper insight into the genetic regulatory mechanisms of kidney development.

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Available from: Stanley Steven Potter
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    • "It has previously been shown that many genes are expressed in more than one developmental stage in the kidney (Brunskill et al., 2008). "
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    ABSTRACT: Wilms' tumours, paediatric kidney cancers, are the archetypal example of tumours caused through the disruption of normal development. The genetically best defined subgroup of Wilms' tumours is the group caused by biallelic loss of the WT1 tumour suppressor gene. Here we describe a developmental series of mouse models with conditional loss of Wt1 in different stages of nephron development before and after the mesenchymal to epithelial transition (MET). We demonstrate that Wt1 is essential for normal development at all kidney developmental stages under study. Comparison of genome-wide expression data from the mutant mouse models to human tumour material of WT1-mutant and WT1 wild-type datasets identifies the stage of origin of human WT1-mutant tumours, and emphasizes fundamental differences between the two human tumour groups due to different developmental stages of origin. © 2015. Published by The Company of Biologists Ltd.
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    • "A few thousand in situ hybridizations were carried out. In addition, however, the diverse compartments of the kidney were gene expression profiled using a combination of laser capture microdissection (LCM) and microarrays (Brunskill et al., 2008) as well as RNA-seq (Brunskill et al., 2011a; Brunskill et al., 2011b; Brunskill and Potter, 2010; Brunskill et al., 2011c). The results define the changing waves of gene expression as the kidney progenitor cells progress through the different stages of nephrogenesis. "
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    • "The nephron progenitor cells (also known as cap mesenchyme [CM] cells) are a subset of the MM cells, which condense around the UB tips beginning at approximately embryonic day 11.5 (E11.5) in the mouse, shortly after the UB invades the MM and begins to branch. Under the control of signals from the UB tips, the CM cells proliferate extensively, thereby self-renewing, while giving rise to nephrons through a complex process that includes aggregation, epithelialization, tubular folding and elongation , segmentation, and cell differentiation (Brunskill et al., 2008; Carroll et al., 2005; Georgas et al., 2009; Kopan et al., 2007; Mugford et al., 2009). New nephrons are generated continuously during kidney development, in concert with the branching of the UB, until about postnatal day 3 (P3), when the nephron progenitors stop self-renewing and differentiate into a final round of nephrons (Brunskill et al., 2011; Hartman et al., 2007; Rumballe et al., 2011). "
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