TY - JOUR
T1 - Planar cell polarity genes Celsr1 and Vangl2 are necessary for kidney growth, differentiation, and rostrocaudal patterning
AU - Brzóska, Hortensja
AU - d'Esposito, Angela M.
AU - Kolatsi-Joannou, Maria
AU - Patel, Vishal
AU - Igarashi, Peter
AU - Lei, Yunping
AU - Finnell, Richard H.
AU - Lythgoe, Mark F.
AU - Woolf, Adrian S.
AU - Papakrivopoulou, Eugenia
AU - Long, David A.
N1 - Publisher Copyright:
© 2016 International Society of Nephrology
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - kidney development
KW - planar cell polarity
KW - renal malformations
KW - rostrocaudal patterning
KW - ureteric branching
UR - http://www.scopus.com/inward/record.url?scp=84991977806&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991977806&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2016.07.011
DO - 10.1016/j.kint.2016.07.011
M3 - Article
C2 - 27597235
AN - SCOPUS:84991977806
SN - 0085-2538
VL - 90
SP - 1274
EP - 1284
JO - Kidney international
JF - Kidney international
IS - 6
ER -