The fully linked HTML version of this article has now been published.
Development ePress online publication date 27 Jul 2005
doi: 10.1242/dev.01944
Research article
FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons
Uta Grieshammer,
Cristina Cebrián,
Roger Ilagan,
Erik Meyers,
Doris Herzlinger*,
and
Gail R. Martin
* Author for correspondence (e-mail: daherzli{at}med.cornell.edu)
During kidney morphogenesis, the formation of nephrons begins when mesenchymal nephron progenitor cells aggregate and transform into epithelial vesicles that elongate and assume an S-shape. Cells in different regions of the S-shaped body subsequently differentiate into the morphologically and functionally distinct segments of the mature nephron. Here, we have used an allelic series of mutations to determine the role of the secreted signaling molecule FGF8 in nephrogenesis. In the absence of FGF8 signaling, nephron formation is initiated, but the nascent nephrons do not express Wnt4 or Lim1, and nephrogenesis does not progress to the S-shaped body stage. Furthermore, the nephron progenitor cells that reside in the peripheral zone, the outermost region of the developing kidney, are progressively lost. When FGF8 signaling is severely reduced rather than eliminated, mesenchymal cells differentiate into S-shaped bodies. However, the cells within these structures that normally differentiate into the tubular segments of the mature nephron undergo apoptosis, resulting in the formation of kidneys with severely truncated nephrons consisting of renal corpuscles connected to collecting ducts by an abnormally short tubular segment. Thus, unlike other FGF family members, which regulate growth and branching morphogenesis of the collecting duct system, Fgf8 encodes a factor essential for gene regulation and cell survival at distinct steps in nephrogenesis.
This article has been cited by other articles:
|
|
|
|
 
M. A. Basson, D. Echevarria, C. Petersen Ahn, A. Sudarov, A. L. Joyner, I. J. Mason, S. Martinez, and G. R. Martin
Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development
Development,
March 1, 2008;
135(5):
889 - 898.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Olsen, L. Funke, J.-f. Long, M. Fukata, T. Kazuta, J. C. Trinidad, K. A. Moore, H. Misawa, P. A. Welling, A. L. Burlingame, et al.
Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice
J. Cell Biol.,
October 8, 2007;
179(1):
151 - 164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Reggiani, D. Raciti, R. Airik, A. Kispert, and A. W. Brandli
The prepattern transcription factor Irx3 directs nephron segment identity
Genes & Dev.,
September 15, 2007;
21(18):
2358 - 2370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-S. Park, M. T. Valerius, and A. P. McMahon
Wnt/{beta}-catenin signaling regulates nephron induction during mouse kidney development
Development,
July 1, 2007;
134(13):
2533 - 2539.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Pajni-Underwood, C. P. Wilson, C. Elder, Y. Mishina, and M. Lewandoski
BMP signals control limb bud interdigital programmed cell death by regulating FGF signaling
Development,
June 15, 2007;
134(12):
2359 - 2368.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-S. Kim, M. S. Kim, A. L. Hancock, J. C. P. Harper, J. Y. Park, G. Poy, A. O. Perantoni, M. Cam, K. Malik, and S. B. Lee
Identification of Novel Wilms' Tumor Suppressor Gene Target Genes Implicated in Kidney Development
J. Biol. Chem.,
June 1, 2007;
282(22):
16278 - 16287.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Narlis, D. Grote, Y. Gaitan, S. K. Boualia, and M. Bouchard
Pax2 and Pax8 Regulate Branching Morphogenesis and Nephron Differentiation in the Developing Kidney
J. Am. Soc. Nephrol.,
April 1, 2007;
18(4):
1121 - 1129.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-T. Cheng, M. Kim, M. T. Valerius, K. Surendran, K. Schuster-Gossler, A. Gossler, A. P. McMahon, and R. Kopan
Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron
Development,
February 15, 2007;
134(4):
801 - 811.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yamaguchi, S. Yonemura, and S. Takada
Grainyhead-related transcription factor is required for duct maturation in the salivary gland and the kidney of the mouse
Development,
December 1, 2006;
133(23):
4737 - 4748.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ikeya, M. Kawada, H. Kiyonari, N. Sasai, K. Nakao, Y. Furuta, and Y. Sasai
Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis
Development,
November 15, 2006;
133(22):
4463 - 4473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dziarmaga, P.-A. Hueber, D. Iglesias, N. Hache, A. Jeffs, N. Gendron, A. MacKenzie, M. Eccles, and P. Goodyer
Neuronal apoptosis inhibitory protein is expressed in developing kidney and is regulated by PAX2
Am J Physiol Renal Physiol,
October 1, 2006;
291(4):
F913 - F920.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Ilagan, R. Abu-Issa, D. Brown, Y.-P. Yang, K. Jiao, R. J. Schwartz, J. Klingensmith, and E. N. Meyers
Fgf8 is required for anterior heart field development
Development,
June 15, 2006;
133(12):
2435 - 2445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lu, G. Minowada, and G. R. Martin
Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function
Development,
January 1, 2006;
133(1):
33 - 42.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. O. Perantoni, O. Timofeeva, F. Naillat, C. Richman, S. Pajni-Underwood, C. Wilson, S. Vainio, L. F. Dove, and M. Lewandoski
Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development
Development,
September 1, 2005;
132(17):
3859 - 3871.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2005
