The vertebrate ocular lens undergoes a spatially defined pattern of di
fferentiation which may be regulated by the ocular distribution of pro
teins from the fibroblast growth factor (FGF) family. The ability of a
ltered FGF-1 (acidic FGF) distribution to disrupt the normal pattern o
f lens differentiation was evaluated by the production of transgenic m
ice which express FGF-1 under the control of the lens-specific alpha A
-crystallin promoter. Since FGF-1 lacks a classical signal peptide con
sensus sequence, transgenic mice were also produced with a chimeric co
nstruct containing the signal peptide sequence of the FGF-4 gene fused
in frame to the coding sequences of the FGF-1 cDNA in order to obtain
extracellular expression of the transgene. The presence of transgenic
mRNA and protein was confirmed by in situ hybridization, Western anal
ysis and immunohistochemistry. The ocular histology of newborn and you
ng adult transgenic mice expressing FGF-1 without a signal peptide app
eared normal. In contrast, mice expressing secreted FGF-I exhibited le
ns abnormalities including the elongation of anterior epithelial cells
. Epithelial cell elongation was accompanied by expression of the fibe
r cell differentiation marker, beta-crystallin. These observations pro
vide an in vivo demonstration that FGF-1 can induce anterior lens epit
helial cells to express characteristics consistent with the onset of f
iber cell differentiation. The transgenic induction of differentiation
confirms that normal lens morphology reflects an asymmetric distribut
ion of inductive factors within the eye.