DURA-MATER SECRETES SOLUBLE HEPARIN-BINDING FACTORS REQUIRED FOR CRANIAL SUTURE MORPHOGENESIS

Cranial sutures play a critical role in calvarial morphogenesis, servi ng as bone growth centers during skull enlargement. Defective suture m orphogenesis, resulting in premature osseous obliteration of sutures a nd their failure to function appropriately, causes severe craniofacial anomalies. Previously published data demonstrated osseous obliteratio n of coronal sutures in vitro in the absence of dura mater and the res cue of sutures from osseous obliteration in rudiments cocultured with dura mater on the opposite sides of 0.45-mu m polycarbonate filters. W ith this in vitro culture system, experiments were designed to examine the nature of the soluble signal secreted by dura mater, required for maintaining intact sutures. The signal remained active in conditioned medium produced from dura mater, which was capable of rescuing corona l sutures from osseous obliteration in calvaria cultured without dura mater. When conditioned medium was segregated into heparin binding and non-heparin-binding fractions, the signal capable of maintaining inta ct coronal sutures cosegregated with the heparin-binding component and remained functional in the absence of the non-heparin-binding compone nt of conditioned medium. Evidence indicates that soluble, heparin-bin ding factors secreted by the dura mater act as osteoinhibitory signals at the suture site.