A. Trumpp et al., Cre-mediated gene inactivation demonstrates that FGF8 is required for cellsurvival and patterning of the first branchial arch, GENE DEV, 13(23), 1999, pp. 3136-3148
In mammals, the first branchial arch (BA1) develops into a number of cranio
facial skeletal elements including the jaws and teeth. Outgrowth and patter
ning of BA1 during early embryogenesis is thought to be controlled by signa
ls from its covering ectoderm. Here we used Cre/loxP technology to inactiva
te the mouse Fgf8 gene in this ectoderm and have obtained genetic evidence
that FGF8 has a dual function in BA1: it promotes mesenchymal cell survival
and induces a developmental program required for BA1 morphogenesis. Newbor
n mutants lack most BA1-derived structures except those that develop from t
he distal-most region of BA1, including lower incisors. The data suggest th
at the BA1 primordium is specified into a large proximal region that is con
trolled by FGF8, and a small distal region that depends on other signaling
molecules for its outgrowth and patterning. Because the mutant mice resembl
e humans with first arch syndromes that include agnathia, our results raise
the possibility that some of these syndromes are caused by mutations that
affect FGF8 signaling in BA1 ectoderm.