title: Early B-cell factor 1 is an essential transcription factor for postnatal glomerular maturation.
abstract: The coordination of multiple cytokines and transcription factors with their downstream signaling pathways has been shown to be integral to nephron maturation. Here we present a completely novel role for the helix-loop-helix transcription factor Early B-cell factor 1 (Ebf1), originally identified for B-cell maturation, for the proper maturation of glomerular cells from mesenchymal progenitors. The expression of Ebf1 was both spatially and temporally regulated within the developing cortex and glomeruli. Using Ebf1-null mice, we then identified biochemical, metabolic, and histological abnormalities in renal development that arose in the absence of this transcription factor. In the Ebf1 knockout mice, the developed kidneys show thinned cortices and reduced glomerular maturation. The glomeruli showed abnormal vascularization and severely effaced podocytes. The mice exhibited early albuminuria and elevated blood urea nitrogen levels. Moreover, the glomerular filtration rate was reduced >66% and the expression of podocyte-derived vascular endothelial growth factor A was decreased compared with wild-type control mice. Thus, Ebf1 has a significant and novel role in glomerular development, podocyte maturation, and the maintenance of kidney integrity and function.
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Fretz
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Nelson
authors.affiliation: Department of Internal Medicine-Nephrology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Heino
authors.initials: H
authors.lastname: Velazquez
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Yougen
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Gilbert W
authors.initials: GW
authors.lastname: Moeckel
authors.affiliation: Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Horowitz
mesh_terms: D000367:Age Factors; D000419:Albuminuria / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001806:Blood Urea Nitrogen; D002454:Cell Differentiation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D005919:Glomerular Filtration Rate; D007678:Kidney Glomerulus / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038081:Organogenesis; D010641:Phenotype; D050199:Podocytes / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C489921:Ebf1 protein, mouse; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse