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 ) used a Pax3-Cre construct to conditionally delete FGF8 in the metanephric mesenchyme; Perantoni et al. (see ) 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.
