Pod1 is required in stromal cells for glomerulogenesis.
Pod1 (capsulin/epicardin/Tcf21) is a basic-helix-loop-helix transcription factor that is highly expressed in the mesenchyme of developing organs that include the kidney, lung, gut, and heart. Null Pod1 mice are born but die shortly after birth due to a lack of alveoli in the lungs and cardiac defects. In addition, the kidneys are hypoplastic and demonstrate disrupted branching morphogenesis of the ureteric bud epithelium, a marked reduction in the number of nephrons, a delay in glomerulogenesis, and blood vessel abnormalities. To further dissect the cellular function of Pod1 during kidney development, chimeric mice were generated through aggregations of null Pod1 embryonic stem cells and murine embryos ubiquitously expressing enhanced green fluorescent protein (GFP). Histologic, immunohistochemical, and in situ hybridization analysis of the resulting chimeric offspring demonstrated both cell autonomous and non-cell autonomous roles for Pod1 in the differentiation of specific renal cell lineages that include peritubular interstitial cells and pericytes. Most strikingly, the glomerulogenesis defect was rescued by the presence of wild-type stromal cells, suggesting a non-cell autonomous role for Pod1 in this cell population.
Cui
Shiying
S
The Samuel Lunenfeld Research Institute, Mt Sinai Hospital, Toronto, Ontario, Canada.
Schwartz
Lois
L
Quaggin
Susan E
SE
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002196:Capillaries / Q000166:cytology / Q000196:embryology; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D007678:Kidney Glomerulus / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009399:Nephrons / Q000166:cytology / Q000196:embryology; D011993:Recombinant Fusion Proteins; D012079:Renal Circulation / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C112923:Tcf21 protein, mouse