In vivo modulation of FGF biological activity alters cranial suture fate.
Gain-of-function mutations in fibroblast growth factor receptors have been identified in numerous syndromes associated with premature cranial suture fusion. Murine models in which the posterior frontal suture undergoes programmed fusion after birth while all other sutures remain patent provide an ideal model to study the biomolecular mechanisms that govern cranial suture fusion. Using adenoviral vectors and targeted in utero injections in rats, we demonstrate that physiological posterior frontal suture fusion is inhibited using a dominant-negative fibroblast growth factor receptor-1 construct, whereas the normally patent coronal suture fuses when infected with a construct that increases basic fibroblast growth factor biological activity. Our data may facilitate the development of novel, less invasive treatment options for children with craniosynostosis.
Greenwald
J A
JA
Laboratory of Developmental Biology and Repair, The Institute of Reconstructive Plastic Surgery, and The Department of Surgery, New York University Medical Center, New York, USA.
Mehrara
B J
BJ
Spector
J A
JA
Warren
S M
SM
Fagenholz
P J
PJ
Smith
L E
LE
Bouletreau
P J
PJ
Crisera
F E
FE
Ueno
H
H
Longaker
M T
MT
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics; D003393:Cranial Sutures / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D004274:DNA, Recombinant; D004388:Dura Mater / Q000166:cytology / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D008297:Male; D051379:Mice; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D004274:DNA, Recombinant; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D005346:Fibroblast Growth Factors; D003094:Collagen