Basic fibroblast growth factor (FGF-2) is a pleiotropic growth factor detected in many different cells and tissues. Normally synthesized at low levels, FGF-2 is elevated in various pathologies, most notably in cancer and injury repair. To investigate the effects of elevated FGF-2, the human full-length cDNA was expressed in transgenic mice under control of a phosphoglycerate kinase promoter. Overexpression of FGF-2 caused a variety of skeletal malformations including shortening and flattening of long bones and moderate macrocephaly. Comparison by Western blot of FGF-2 transgenic mice to nontransgenic littermates showed expression of human FGF-2 protein in all major organs and tissues examined including brain, heart, lung, liver, kidney, spleen, and skeletal muscle; however, different molar ratios of FGF-2 protein isoforms were observed between different organs and tissues. Some tissues preferentially synthesize larger isoforms of FGF-2 while other tissues produce predominantly smaller 18-kDa FGF-2. Translation of the high molecular weight isoforms initiates from unconventional CUG codons and translation of the 18-kDa isoform initiates from an AUG codon in the FGF-2 mRNA. Thus the Western blot data from the FGF-2 transgenic mice suggest that tissue-specific expression of FGF-2 isoforms is regulated translationally.

The currently accepted description of the pattern of electromyographic (EMG) activity in the pharyngeal swallow is that reported by Doty and Bosma in 1956; however, those authors describe high levels of intramuscle and of interindividual EMG variation. We reinvestigated this pattern, testing two hypotheses concerning EMG variation: 1) that it could be reduced with modern methodology and 2) that it could be explained by selective detection of different types of motor units. In eight decerebrate infant pigs, we elicited radiographically verified pharyngeal swallows and recorded EMG activity from a total of 16 muscles. Synchronization signals from the video-radiographic system allowed the EMG activity associated with each swallow to be aligned directly with epiglottal movement. The movements were highly stereotyped, but the recorded EMG signals were variable at both the intramuscle and interanimal level. During swallowing, some muscles subserved multiple functions and contained different task units; there were also intramuscle differences in EMG latencies. In this situation, statistical methods were essential to characterize the overall patterns of EMG activity. The statistically derived multimuscle pattern approximated to the classical description by Doty and Bosma (Doty RW, Bosma JF. J Neurophysiol 19: 44-60, 1956) with a leading complex of muscle activities. However, the mylohyoid was not active earlier than other muscles, and the geniohyoid muscle was not part of the leading complex. Some muscles, classically considered inactive, were active during the pharyngeal swallow.

To investigate the effects of protein malnutrition on a normal growth trajectory, we radiographed Rattus norvegicus from 22 d (weaning) and continuing past adult size. We took measurements from longitudinal radiographs of rats fed a control diet and littermates fed an isocaloric low protein experimental diet. A Gompertz model was fit to each individual rat for body weight and 22 measurements of the craniofacial skeleton, producing parameters that described the rate and timing of growth. We tested for differences in these parameters due to diet, sex and litter with a mixed-model three-way ANOVA. Allometric analysis examined the scaling relationships between and within various regions of the skull. For most measurements, final sizes predicted by the model were not significantly different between rats fed the two diets, although the differences in final measurements showed small, but significant differences in growth between rats in the two diet groups. The instantaneous initial rate of growth, maximum rate of growth and deceleration of growth were significantly higher in the control rats for every measurement. Rats fed the low protein diet grew for a significantly longer period of time. The shape of the neurocranium was relatively conserved between diet groups; however, rats fed the low protein diet had shorter and relatively wider skulls than the controls. These results suggest that functional demands of the viscerocranium were greater after birth, and that growth in this area was faster. The viscerocranium reached functional adult proportions earlier and was therefore more susceptible to epigenetic perturbations such as dietary protein level. Protein malnutrition did not affect many aspects of adult size, but strongly altered the growth trajectory to achieve that size.

Evolutionary time has a characteristic direction as demonstrated by the asymmetry of clade diversity diagrams in large statistical samples. Evolutionary groups generally concentrate diversity during their early histories, producing a preponderance of bottom-heavy clades among those that arise early in the history of a larger group. This pattern holds across taxonomic levels and across differences in anatomy and ecology (marine invertebrates, terrestrial mammals). The quantitative study of directionality in life's history (replacing vague, untestable, and culturally laden notions of "progress") should receive more attention from paleobiologists.

New World monkeys vary considerably in the manner and degree to which they use their tails. There ought to arise a corresponding variation in the stresses on caudal vertebrae. Consequently, different behavior types will have contrasting caudal morphologies. This study investigates caudal morphology of several New World monkeys representing the large range of ability from totally nonprehensile tails to the dexterous fifth limb of spider monkeys. One large-bodied, nonprehensile-tailed Old World monkey is included to offset the correlation between size and degree of prehensility in New World monkeys. These monkeys vary both within and between species as to the number of caudal vertebrae and the length of individual vertebrae. Despite this variation, the length of caudal vertebrae within a given tail decreases at a constant rate across species. The width of the vertebrae at two points, midbone and the proximal end, separates the monkeys with prehensile tails from those with nonprehensile tails. The middle of the vertebrae is wider and more robust in prehensile-tailed forms. This is associated with stronger bones in tails subject to greater stress. THe proximal width of each bone is also greater in the prehensile-tailed monkeys. This measure reflects the lateral development of the proximal transverse process. This provides a larger lever arm for M. caudalis lateralis, implying greater rotational ability.

Specialization for a locomotor behaviour may affect limb bone morphology throughout ontogeny. Ontogenetic development of the limb skeletons of two mammalian species, which are behaviourally specialized for the half-bounding gait (Chinchilla lanigera and Oryctolagus cuniculus), were compared to two similarly-sized species which are not specialized for half-bounding (Rattus norvegicus and Monodelphis domestica). Limb bone lengths and anteroposterior diameters (mediolateral diameters for the radius and metacarpal) were measured from radiographs taken throughout the ontogeny of each species. Body mass was also measured repeatedly during growth. Bone measurements were regressed against body mass, as well as forelimb bone length vs serially homologous hindlimb bone length, bone length vs total limb length and bone length vs width. Similar comparisons were made among adults of each species using ratios. Although there were many signi®cant differences among species, overall there were few consistent differences in adult scaling ratios or ontogenetic allometry slopes between specialized and generalized groups. Adult specialized half-bounders had signi®cantly narrower tibiae and metatarsals than the gaitgeneralized runners. Specialized half-bounders usually had similar slopes for hindlimb length vs width ontogenetic comparisons, but the non-specialized species did not group together. However, there were two patterns that occurred among all four species: (1) hindlimb bone lengths nearly always grew faster than the serially homologous forelimb bone lengths in all species; (2) proximal elements usually increased in length proportionally faster than distal elements. In conclusion, small mammals may share strong developmental constraints that govern their relative growth rates. It is also likely that there are different selective pressures on juveniles and adults, but that these selective pressures may not be different between specialized and unspecialized runners during ontogeny.

Cleft lip and palate (CL /P), as is true of many craniofacial malformations in humans, is etiologically complex and highly variable in expression. A/WySn mice are an intriguing model for human CL/P because they develop this dysmorphology with a variable expression pattern, incomplete penetrance and frequent unilateral expression on a homogeneous genetic background. The developmental basis for this variation in expression is unknown, but of great significance for understanding such expression patterns in humans. As a step towards this goal, this study used three-dimensional geometric morphometric and novel high throughput morphometric techniques based on three-dimensional computed microtomography of mouse embryos to analyze craniofacial shape variation during primary palate formation. Our analysis confirmed previous findings based on two-dimensional analyses that the midface in A/WySn embryos, and the maxillary prominence in particular, is relatively reduced in size and appears to be developmentally delayed. In addition, we find that shape variance is increased in A/WySn embryos during primary palate formation compared to both C57BL/6J mice and the F1 crosses between these strains. If the reduction in midfacial growth caused by the Wnt9b hypomorphic mutation pushes A/WySn mice closer on average to the threshold for cleft lip formation, the elevated shape variance may explain why some, but not all, embryos develop the dysmorphology in a genetically homogeneous inbred line of mice.

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