Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch.
In mammals, the first branchial arch (BA1) develops into a number of craniofacial skeletal elements including the jaws and teeth. Outgrowth and patterning of BA1 during early embryogenesis is thought to be controlled by signals from its covering ectoderm. Here we used Cre/loxP technology to inactivate 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. Newborn mutants lack most BA1-derived structures except those that develop from the distal-most region of BA1, including lower incisors. The data suggest that the BA1 primordium is specified into a large proximal region that is controlled by FGF8, and a small distal region that depends on other signaling molecules for its outgrowth and patterning. Because the mutant mice resemble 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.
Trumpp
A
A
G.W. Hooper Foundation, Department of Microbiology, School of Medicine, University of California at San Francisco (UCSF), San Francisco, California 94143-0552, USA.
Depew
M J
MJ
Rubenstein
J L
JL
Bishop
J M
JM
Martin
G R
GR
D000818:Animals; D001934:Branchial Region / Q000502:physiology*; D002470:Cell Survival; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D007180:Incisor / Q000196:embryology; D019426:Integrases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007569:Jaw Abnormalities / Q000196:embryology / Q000235:genetics; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014071:Tooth Abnormalities / Q000196:embryology / Q000235:genetics; D014764:Viral Proteins
C496457:Fgf8 protein, mouse; D014764:Viral Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; C045073:Cre recombinase; D019426:Integrases