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. Author manuscript; available in PMC: 2011 Oct 9.
Published in final edited form as: Pediatr Nephrol. 2010 Jan 5;25(6):1005–1016. doi: 10.1007/s00467-009-1392-6

Table 1.

Gene expression profiling of human and murine kidney development

Article title Technologya Experiment Source/species Outcome Reference
Screen for genes regulated
  during early kidney
  morphogenesis		 Transfilter organ
  culture and ddPCR		 Spatial E11 cultured mesenchymal cells
  from wildtype outbred CD1
  mice		 Compared uninduced state to that
  of explants cultured with spinal
  cord; 5/13 known genes and
  4/8 novel gene tags verified by
  Northern blot and ISH		 [5]
Mesenchymal-epithelial
  transition in the
  developing metanephric
  kidney: gene expression
  study by differential
  display		 ddPCR, ISH validation Spatial E13 cultured MM, F344 rat Induced metanephric explants vs.
  tubular induced explants; 72
  differentially regulated mRNAs
  detected in a MET event		 [6]
Changes in global gene
  expression patterns
  during development and
  maturation of the rat
  kidney		 Affymetrix Rat
  Genome U34A
  GeneChip Array;
  custom data analysis
  with “The Equaliser”
  & “eBlot”		 Temporal Isolated RNA from E13, 15, 17,
  19, P0, P7 and NP adult rats		 873/8740 genes were found to
  vary significantly (P = 0.0025)
  during rat kidney development.
  These genes clustered into five
  clear patterns of gene
  expression, each defined by a
  unique cluster-member gene
  function, tissue distribution,
  and embryonic expression		 [7]
Microarray analysis of
  novel cell lines
  representing two stages of
  metanephric mesenchyme
  differentiation		 Affymetrix Mu6500,
  Mu11K and U74A
  chip sets, ISH
  validation		 Spatial Clonal kidney cell lines of
  representative stages of
  uninduced and induced MM
  isolated from Hoxa11/SV40 4–
  12 week old transgenic mice		 Microarray experiments were
  performed on representative
  stages of MM (mK3 early =
  prior to induction) and late mK4
  (post-induction on way to MET);
  121 differential genes showed
  >10fold difference in
  expression; identification of
  genes not previously implicated
  in MM differentiation. (Hoxa7,
  Notch1, Fst, Igf2, sFRP1,
  Cdh16, shrom, Prx1, EST
  AA123934, NfiB)		 [8]
A catalogue of gene
  expression in the
  developing kidney		 Affymetrix U74Av2,
  ISH validation		 Temporal
  & Spatial		 Microdissected wildtype murine
  UB & MM (E11.5); total
  kidneys E11.5, E12.5 (pooled),
  E13.5, E16.5 & adult
  		 Identification of 428 genes with
  significantly elevated
  expression levels at E12.5 vs.
  adult kidney; 78 genes
  differentially expressed
  between E11.5UB vs. MM; 53
  in UB, 25 in MM		 [10]
Changes in gene
  expression patterns in the
  ureteric bud and
  metanephric mesenchyme
  in models of kidney
  development		 High-density DNA
  arrays together with
  dIVT; Affymetrix Rat
  Genome U34A Gene
  chips		 Temporal
  & Spatial		 In vitro models of isolated E13
  Sprague-Dawley rat UB and
  MM cultures		 in vitro models for
  morphogenesis of the rat UB
  and MM examined and data
  compared to whole embryonic
  kidney at different stages of
  development; 740/8471 genes
  were highly expressed in UB;
  624/8471 genes highly
  expressed in MM		 [12]
Gene expression in the
  normal adult human
  kidney assessed by
  complementary DNA
  microarray		 41,859 unique cDNA
  array (Stanford
  Functional Genomics
  Facility), IHC
  validation		 Spatial Human nephrectomy specimens
  removed for renal neoplasia,
  lobes separated and dissected
  into 5 fractions		 RNA isolated from inner and
  outer cortex, inner and outer
  medulla, papillary tips, renal
  pelvis and glomeruli. cDNA
  microarray & IHC validation;
  1548/41859 genes with
  variable expression; distinct
  expression of >250 genes in
  cortex, 139 in glomerulus, 130
  genes in renal tubules, 58
  genes in medullary vs.
  papillary tips, 102 genes in
  papillary tips/pelvis		 [18]
Identification of kidney
  mesenchymal genes by a
  combination of
  microarray analysis and
  Sall1-GFP knock-in mice		 Affymetrix Murine
  Genome U74v2
  GeneChips, ISH
  validation		 Spatial Isolated murine Sall1-GFP-
  positive population of E17.5
  kidneys		 Compared mesenchymal vs. UB
  derivatives; reported 78% of
  top 50 mRNAs were in the
  mesenchyme; Identification of
  17 novel mesenchymal genes		 [15]
Temporal and spatial
  transcriptional programs
  in murine kidney
  development		 Compugen long-
  oligonucleotide
  microarrays, ISH
  validation		 Temporal
  & Spatial		 Wildtype CD1 murine kidneys
  from 24-h intervals from E10.5
  to P0; E10.5 MM vs. IM;
  E15.5 Hoxb7-GFP positive
  ureteric tree vs. Hoxb7–GFP-
  negative MM		 Temporal: Profiling through
  developmental time course &
  boxed comparison of
  development at E10.5 vs. 11.5
  vs. 13.5 kidneys; functional
  annotation clustered into 5
  classes and pathway/network
  analysis to identify critical
  signaling pathways; Spatial:
  MM E10.5 compared to
  adjacent IM; E15.5 UB vs.
  GFP negative mesenchymal
  derivatives from the Hoxb7
  mouse; 3600 dynamically
  expressed genes identified		 [11]
Novel regulators of kidney
  development from the
  tips of the ureteric bud		 Affymetrix Mouse
  Genome 430 2.0
  Array, RT-PCR and
  ISH validation		 Spatial 13.5 rats, E12.5 mice isolated
  UB & MM		 UB tips vs. tree have distinct
  gene expression profile,
  identified 20 predicted secreted
  protein transcripts upregulated
  in UB vs MM for both rat and
  mouse, e.g. Clf-1		 [14]
Spatial gene expression in
  the T-stage mouse
  metanephros		 Compugen mouse long
  microarrays, ISH
  validation		 Spatial Dissected murine E11.5 ureteric
  tip, ureteric tree and MM		 Identified genes spatially
  expressed in regions of the
  developing kidney e.g. Ureteric
  tip epithelium: sim-1, Arg2,
  Tacstd1, Crlf-1, BMP7; ureteric
  tree epithelium: Innp1, Itm2b,
  Mkrn1, SPARC, Emu2 and
  Gsta3; MM genes: CSPG2 and
  CV-2		 [13]
Microarray interrogation of
  human metanephric
  mesenchymal cells
  highlights potentially
  important molecules in
  vivo		 Affymetrix human
  U133 plus 2.0 Gene
  Chips, RT-PCR and
  IHC validation		 Temporal 10-week gestation human fetus
  used to generate a human MM
  cell line		 Generated mesenchymal cell
  lines from first trimester
  human metanephros and
  stimulated with growth factors;
  36 genes differentially
  regulated; changes in
  components of LIF signaling
  pathway reported		 [58]
Atlas of gene expression in
  the developing kidney at
  microanatomic resolution		 Affymetrix Mouse
  Genome 430 2.0
  Array; ISH validation		 Spatial LCM-or FACS-sorted
  subpopulations from E12.5 and E15.5
  kidneys of CD1, Six2-GFP
  and Meis1-GFP mice.		 Microarray analysis of 14
  subcompartments of the
  developing kidney; 223 genes
  identified as component-
  specific; identification of gene
  expression states of intermediate
  states of nephrogenesis;
  regulatory networks explored		 [19]

ddPCR, Differential display PCR; MET, mesenchyme to epithelial transition; MM, metanephric mesenchyme; IM, intermediate mesoderm; UB, ureteric bud; dIVT, double in vitro transcription; ISH, in situ hybridisation; IHC, immunohistochemistry; LCM, laser capture microdissection; FACS, fluorescence-activated cell sorting; E, embryonic day; GFP, green fluorescent protein

a

Affymetrix, Santa Clara, CA; Compugen, Toronto, ONT, Canada