Birotundal diameter of the human sphenoid bone from age six years to early adulthood

Longitudinal data for a twenty-year period are presented for a dimension of the human sphenoid bone as seen on postero-anterior roentgenograms of 22 males and 18 females (healthy, American-born Caucasoids). Birotundal diameter measured as the distance between the centers of the right and left foramen rotundum averaged near 32.0 mm for each sex at age 6 years. Individual increase in size to age 26 years ranged between 3.2 mm and 8.3 mm. There is no correlation between size at age 6 years and change between this age and early adulthood. For 54 males and 50 females at age 9 years, intercorrelations were obtained among six variables: birotundal diameter, head breadth, bizygomatic diameter, bigonial diameter, upper and loweer dental arch widths at the permanent first molars. The r's were nonsignificant or low positive (with the exception of upper-lower dental arch, r = 0.76). The results of this study are aligned with three previous studies of human cranial base width.     

A note on craniofacial sutural growth

The paper presents and discusses some features of sutural structures. Fibre orientation in sutures seems to be quite variable and associated with minute local growth phenomena. Trabecular patterns in bones, reflecting growth, appear to support the idea of the outside determination of growth. The bevelled and interdigitated structures seen in many sutures may be interpreted as an expedient solution to the problem of fast growth.     

Imaging analysis of mineralocorticoid receptor and importins in single living cells by using GFP color variants

Signaling from the endothelin-A (Ednra) receptor is responsible for initiating multiple signaling pathways within neural crest cells (NCCs). Loss of this initiation is presumably the basis for the craniofacial defects observed in Ednra^–/– embryos. However, it is not known whether continued Ednra signaling in NCC derivatives is required for subsequent development of the lower jaw. To address this question, mice containing loxP recombination sequences flanking a portion of the Ednra gene were bred with transgenic mice that express Cre recombinase under control of a Dlx5/6 enhancer element. We find that while Ednra gene inactivation within the mandibular arch of these Ednra conditional knockout embryos is detectable by embryonic day (E) 10.5, mandibular arch-specific gene expression is normal, as is overall mandible development. These results suggest that while Ednra receptor signaling is crucial for early NCC patterning, subsequent Ednra signaling is not essential for mandible bone development.This work was supported in part by grants from the National Institutes of Health and the American Heart Association to D.E.C.     

Characteristic defects in neural crest cell-specific Galphaq/Galpha11- and Galpha12/Galpha13-deficient mice

The endothelin/endothelin receptor system plays a critical role in the differentiation and terminal migration of particular neural crest cell subpopulations. Targeted deletion of the G-protein-coupled endothelin receptors ET(A) and ET(B) was shown to result in characteristic developmental defects of derivatives of cephalic and cardiac neural crest and of neural crest-derived melanocytes and enteric neurons, respectively. Since both endothelin receptors are coupled to G-proteins of the G(q)/G(11)- and G(12)/G(13)-families, we generated mouse lines lacking Galpha(q)/Galpha(11) or Galpha(12)/Galpha(13) in neural crest cells to study their roles in neural crest development. Mice lacking Galpha(q)/Galpha(11) in a neural crest cell-specific manner had craniofacial defects similar to those observed in mice lacking the ET(A) receptor or endothelin-1 (ET-1). However, in contrast to ET-1/ET(A) mutant animals, cardiac outflow tract morphology was intact. Surprisingly, neither Galpha(q)/Galpha(11)- nor Galpha(12)/Galpha(13)-deficient mice showed developmental defects seen in animals lacking either the ET(B) receptor or its ligand endothelin-3 (ET-3). Interestingly, Galpha(12)/Galpha(13) deficiency in neural crest cell-derived cardiac cells resulted in characteristic cardiac malformations. Our data show that G(q)/G(11)- but not G(12)/G(13)-mediated signaling processes mediate ET-1/ET(A)-dependent development of the cephalic neural crest. In contrast, ET-3/ET(B)-mediated development of neural crest-derived melanocytes and enteric neurons appears to involve G-proteins different from G(q)/G(11)/G(12)/G(13).     

Smad2 and Smad3 coordinately regulate craniofacial and endodermal development

Ligands of the transforming growth factor-beta (TGF-beta) superfamily are involved in numerous developmental and disease processes. TGF-beta, activins, and nodal ligands operate through the highly homologous Smad2 and Smad3 intracellular mediators. Smad2 mutants exhibit early embryonic lethality, while Smad3 mutants are viable, but show a plethora of postnatal phenotypes, including immune dysfunction and skeletal abnormalities. Previously, we have shown that the Smad2 and Smad3 genes function cooperatively during liver morphogenesis. Here we show that Smad2 and Smad3 are required at a full dosage for normal embryonic development. Animals lacking one allele of each gene exhibit a variably penetrant phenotype in which structures in the anterior and ventral midline are reduced or lost; additionally, we demonstrate that this craniofacial defect and the previously reported hepatic phenotypes are both due to defects in the definitive endoderm. A reduction of endodermal gene expression as well as a failure to displace the visceral endoderm occurs despite the formation of a normal foregut pocket. This precedes any defects in anterior patterning and likely causes the abnormalities observed in craniofacial and midline development, as well as hepatogenesis.     

A new origin for the maxillary jaw

One conserved feature of craniofacial development is that the first pharyngeal arch has two components, the maxillary and mandibular, which then form the upper and lower jaws, respectively. However, until now, there have been no tests of whether the maxillary cells originate entirely within the first pharyngeal arch or whether they originate in a separate condensation, cranial to the first arch. We therefore constructed a fate map of the pharyngeal arches and environs with a series of dye injections into stage 13-17 chicken embryos. We found that from the earliest stage examined, the major contribution to the maxillary bud is from post-optic mesenchyme with a relatively minor contribution from the maxillo-mandibular cleft. Cells labeled within the first pharyngeal arch contributed exclusively to the mandibular prominence. Gene expression data showed that there were different molecular codes for the cranial and caudal maxillary prominence. Two of the genes examined, Rarbeta (retinoic acid receptor beta) and Bmp4 (bone morphogenetic protein) were expressed in the post-optic mesenchyme and epithelium prior to formation of the maxillary prominence and then were restricted to the cranial half of the maxillary prominence. In order to determine the derivatives of the maxillary prominence, we performed focal injections of CM-DiI into the stage 24 maxillary prominence. Labeled cells contributed to the maxillary, palatine, and jugal bones, but not the other elements of the upper beak, the premaxilla and prenasal cartilage. We also determined that the cranial cells give rise to more distal parts of the upper beak, whereas caudal cells form proximal structures. Grafts of stage 24 maxillary prominences were also analyzed to determine skeletal derivatives and these results concurred with the DiI maps. These early and later fate maps indicate that the maxillary prominence and its skeletal derivatives are not derived from the first pharyngeal arch but rather from a separate maxillary condensation that occurs between the eye and the maxillo-mandibular cleft. These data also suggest that during evolution, recession of the first pharyngeal arch-derived palatoquadrate cartilage to a more proximal position gave way to the bony upper jaw of amniotes.     

Analysis and visualization of growth-related and treatment-induced craniofacial changes

An analysis and visualization of craniofacial shape changes due to growth or orthodontic treatment is presented. The suggested method is based on an adapted Karhunen-Loève decomposition of time-discrete data based on landmarks in lateral X-rays of the skull. It allows for a reduction of the high-dimensional dynamic problem to a few spatial modes representing synchronous components of growth patterns with time-dependent mode coefficients. The growth-related shape changes as well as the orthodontic treatment effects are visualized by overdrawing the underlying shape changes. The results based on this technique give insight into the still controversially discussed question to which degree the craniofacial skeletal structures can be influenced by orthodontic appliances.