TY - JOUR
T1 - The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment
AU - Cebrian, Cristina
AU - Asai, Naoya
AU - D'Agati, Vivette
AU - Costantini, Frank
N1 - Funding Information:
We thank Zaiqi Wu for technical assistance and Chyuan-Sheng Lin for the CSL3 ESCs. This work was supported by NIH grants R01DK082715 and R01DK083289 to F.C. and a fellowship from the National Kidney Foundation to C.C.
PY - 2014/10/4
Y1 - 2014/10/4
N2 - Nephrons, the functional units of the kidney, develop from progenitor cells (cap mesenchyme [CM]) surrounding the epithelial ureteric bud (UB) tips. Reciprocal signaling between UB and CM induces nephrogenesis and UB branching. Although low nephron number is implicated in hypertension and renal disease, the mechanisms that determine nephron number are obscure. To test the importance of nephron progenitor cell number, we genetically ablated 40% of these cells, asking whether this would limit kidney size and nephron number or whether compensatory mechanisms would allow the developing organ to recover. The reduction in CM cell number decreased the rate of branching, which in turn allowed the number of CM cells per UB tip to normalize, revealing a self-correction mechanism. However, the retarded UB branching impaired kidney growth, leaving a permanent nephron deficit. Thus, the number of fetal nephron progenitor cells is an important determinant of nephron endowment, largely via its effect on UB branching.
AB - Nephrons, the functional units of the kidney, develop from progenitor cells (cap mesenchyme [CM]) surrounding the epithelial ureteric bud (UB) tips. Reciprocal signaling between UB and CM induces nephrogenesis and UB branching. Although low nephron number is implicated in hypertension and renal disease, the mechanisms that determine nephron number are obscure. To test the importance of nephron progenitor cell number, we genetically ablated 40% of these cells, asking whether this would limit kidney size and nephron number or whether compensatory mechanisms would allow the developing organ to recover. The reduction in CM cell number decreased the rate of branching, which in turn allowed the number of CM cells per UB tip to normalize, revealing a self-correction mechanism. However, the retarded UB branching impaired kidney growth, leaving a permanent nephron deficit. Thus, the number of fetal nephron progenitor cells is an important determinant of nephron endowment, largely via its effect on UB branching.
UR - https://www.scopus.com/pages/publications/84898028444
UR - https://www.scopus.com/pages/publications/84898028444#tab=citedBy
U2 - 10.1016/j.celrep.2014.02.033
DO - 10.1016/j.celrep.2014.02.033
M3 - Article
C2 - 24656820
AN - SCOPUS:84898028444
SN - 2211-1247
VL - 7
SP - 127
EP - 137
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -