Planar cell polarity genes Celsr1 and Vangl2 are necessary for kidney growth, differentiation, and rostrocaudal patterning.
The mammalian kidney contains nephrons comprising glomeruli and tubules joined to ureteric bud-derived collecting ducts. It has a characteristic bean-like shape, with near-complete rostrocaudal symmetry around the hilum. Here we show that Celsr1, a planar cell polarity (PCP) gene implicated in neural tube morphogenesis, is required for ureteric tree growth in early development and later in gestation prevents tubule overgrowth. We also found an interaction between Celsr1 and Vangl2 (another PCP gene) in ureteric tree growth, most marked in the caudal compartment of the kidneys from compound heterozygous mutant mice with a stunted rump. Furthermore, these genes together are required for the maturation of glomeruli. Interestingly, we demonstrated patients with CELSR1 mutations and spina bifida can have significant renal malformations. Thus, PCP genes are important in mammalian kidney development and have an unexpected role in rostrocaudal patterning during organogenesis.
Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
Hortensja Ł
HŁ
Brzóska
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, UK.
Angela M
AM
d'Esposito
Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
Maria
M
Kolatsi-Joannou
Department of Internal Medicine, University of Texas Southwestern School of Medicine, Dallas, Texas, USA.
Vishal
V
Patel
Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Peter
P
Igarashi
Dell Pediatric Research Institute, Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas, USA.
Yunping
Y
Lei
Dell Pediatric Research Institute, Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas, USA.
Richard H
RH
Finnell
Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, UK.
Mark F
MF
Lythgoe
Institute of Human Development, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Adrian S
AS
Woolf
Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK. Electronic address: e.papakrivopoulou@ucl.ac.uk.
Eugenia
E
Papakrivopoulou
Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK. Electronic address: d.long@ucl.ac.uk.
David A
DA
Long
D000818:Animals; D016764:Cell Polarity / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000196:embryology* / Q000473:pathology; D008809:Mice, Inbred C3H; D009419:Nerve Tissue Proteins / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D016135:Spinal Dysraphism / Q000473:pathology*
C117380:Celsr1 protein, mouse; C431577:Ltap protein, mouse; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled
kidney development; planar cell polarity; renal malformations; rostrocaudal patterning; ureteric branching