First published online August 11, 2005
Development 132, 1702e (2005)
© The Company of Biologists Limited
Deciphering FGF8 functions in development
Fibroblast growth factors (FGFs) are involved in many key developmental
events but deciphering what each FGF does during development can be a
challenge. New findings, however, now reveal that FGF8 is essentially required
for gene regulation and cell survival during mouse kidney development. As FGF8
is essential for gastrulation, a conditional knockout approach was needed to
investigate the involvement of FGF8 in kidney development. Grieshammer et al.
(see p. 3847) used a
Pax3-Cre construct to conditionally delete FGF8 in the metanephric
mesenchyme; Perantoni et al. (see
p. 3859) used a
Brachyury T-Cre construct to generate mice in which Fgf8 is
conditionally deleted in all mesodermal cells. Unexpectedly, given previous
research in chicks, Perantoni et al. found that FGF8 is not essential for
somatic segmentation or differentiation, or for limb bud initiation. However,
the Fgf8 conditional-null mice of both groups were born with severely
deformed kidneys; although nephron formation is initiated in mutant embryos,
nephrogenesis is blocked between the renal vesicle and S-shaped body stages of
development. FGF8 deficiency also caused aberrant cell death within the
cortical nephrogenic zone, the region of the developing kidney that provides
progenitor cells for nephron formation. Both groups also report that FGF8 acts
in combination with WNT4 to sustain Lim1 expression, which is needed
for normal nephrogenesis. Finally, when Grieshammer et al. analysed the
consequences of reducing rather than eliminating FGF8 function – by
studying mice carrying a hypomorphic allele of Fgf8 – they
found that although mesenchymal cells now differentiated into S-shaped bodies,
they then apoptosed, resulting in kidneys with severely truncated nephrons.
Thus, the groups conclude that FGF8 is essential for gene regulation and cell
survival at distinct stages of nephrogenesis.
Related articles in Development:
- 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
Development 2005 132: 3847-3857.
[Abstract]
[Full Text]
- Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development
- Alan O. Perantoni, Olga Timofeeva, Florence Naillat, Charmaine Richman, Sangeeta Pajni-Underwood, Catherine Wilson, Seppo Vainio, Lee F. Dove, and Mark Lewandoski
Development 2005 132: 3859-3871.
[Abstract]
[Full Text]
