Facial development and type III collagen RNA expression: Concurrent repression in the osteopetrotic (Toothless, tl) rat and rescue after treatment with colony-stimulating factor-1

The toothless (osteopetrotic) mutation in the rat is characterized by retar ded development of the anterior facial skeleton. Growth of the anterior fac e in rats occurs at the premaxillary-maxillary suture (PMMS). To identify p otential mechanisms for stunted facial growth in this mutation we compared the temporospatial expression of collagen I (Col I) and collagen III (Col I II) RNA around this suture in toothless (tl) rats and normal littermates by in situ hybridization of specific riboprobes in sagittal sections of the h ead. In normal rats, the suture is S shaped at birth and becomes highly con voluted by 10 days with cells in the center (fibroblasts and osteoblast pro genitors) expressing Col III RNA and those at the periphery (osteoblasts) e xpressing no Col III RNA but high amounts of Col I RNA throughout the growt h phase (the first 2 postnatal weeks). In the mutant PMMS, cells were reduc ed in number, less differentiated, and fewer osteoblasts were encountered. Expression of Col I RNA was at normal levels, but centrosutural cells expre ssed Col III RNA only after day 6 and then only weakly. A highly convoluted sutural shape was never achieved in mutants during the first 2 postnatal w eeks. Treatment of tl rats with the cytokine CSF-1 improved facial growth a nd restored cellular diversity and Col III RNA expression in the PMMS to no rmal levels. Taken together, these data suggest that normal facial growth i n rats is related to expression of Col III RNA by osteoblast precursors in the PMMS, that these cells are deficient in the tl mutation and are rescued following treatment with CSF-1, Dev Dyn 1999;215:117-125, (C) 1999 Wiley L iss, Inc.