Spatial and temporal distribution of cellular proliferation in the cranialbase of normal and midfacially retrusive mice

The craniofacial region of the Brachyrrhine (Br) mouse is characterized by a retruded midface. The cellular mechanism causing this growth deficiency i s unknown. However, the cranial base is foreshortened in adult BI mice. The purpose of this study was to determine whether the spatial and temporal pa tterns of cellular proliferation in the cranial base (CB) differ between no rmal (C3H/HeJ) and Br mutant (3H1 Br/+) embryonic mice. Twenty-four dams we re injected H-3 thymidine (5 mu Ci/gram body weight) and 15 embryos from ea ch group were collected at Theiler stages 23, 25, and 27 (15, 17, and 19 da ys of gestation). Serial sections from each head were processed with routin e autoradiography. Labelling indices (LI) were determined for each specimen and cellular proliferation maps were generated for each age group. LI patt erns within and between groups were compared statistically. Results showed that cellular proliferation in the CB of normal embryos displayed a time- a nd position-dependent pattern, characteristic of transient growth sites (TG S). Generally, as age increases, cellular proliferative activities decrease gradually (from an average LI of 11.4 +/- 5.7% at stage 23 to 4.4 +/- 2.2% at stage 27), and the number of the TGS decreases in the presumptive nasal septal region and increases in presumptive sphenoethmoidal area with age, indicating the existence of cellular subpopulations in the CB. Cellular pro liferation in the CB of the Br mutant displays a different growth pattern c ompared to the normal condition. Deficiencies in cellular proliferation exi st mainly in the presumptive sphenoethmoidal area of the CB. The results in dicate that the TGS play an important role in the normal morphogenesis of t he CB, and abnormalities in their timing and/or position may be responsible for the dysmorphology of the midface in the Br mutant. Clin. Anat. 12.315- 325, 1999. (C) 1999 Wiley-Liss, Inc.