The Interaction of Genetic Background and Mutational Effects in Regulation of Mouse Craniofacial Shape.

Inbred genetic background significantly influences the expression of phenotypes associated with known genetic perturbations and can underlie variation in disease severity between individuals with the same mutation. However, the effect of epistatic interactions on the development of complex traits, such as craniofacial morphology, is poorly understood. Here, we investigated the effect of three inbred backgrounds (129X1/SvJ, C57BL/6J, and FVB/NJ) on the expression of craniofacial dysmorphology in mice (Mus musculus) with loss of function in three members of the Sprouty family of growth factor negative regulators (Spry1, Spry2, or Spry4) in order to explore the impact of epistatic interactions on skull morphology. We found that the interaction of inbred background and the Sprouty genotype explains as much craniofacial shape variation as the Sprouty genotype alone. The most severely affected genotypes display a relatively short and wide skull, a rounded cranial vault, and a more highly angled inferior profile. Our results suggest that the FVB background is more resilient to Sprouty loss of function than either C57 or 129, and that Spry4 loss is generally less severe than loss of Spry1 or Spry2 While the specific modifier genes responsible for these significant background effects remain unknown, our results highlight the value of intercrossing mice of multiple inbred backgrounds to identify the genes and developmental interactions that modulate the severity of craniofacial dysmorphology. Our quantitative results represent an important first step toward elucidating genetic interactions underlying variation in robustness to known genetic perturbations in mice

Mouse Models and the Evolutionary Developmental Biology of the Skull

Understanding development is relevant to understanding evolution because developmental processes structure the expression of phenotypic variation upon which natural selection acts. Advances in developmental biology are fueling a new synthesis of developmental and evolutionary biology, but it remains unclear how to use developmental information that largely derives from a few model organisms to test hypotheses about the evolutionary developmental biology of taxa such as humans and other primates that have not been or are not amenable to direct study through experimental developmental biology. In this article, we discuss how and when model organisms like mice are useful for studying the evolutionary developmental biology of even rather distantly related and morphologically different groups like primates. A productive approach is to focus on processes that are likely to play key roles in producing evolutionarily significant phenotypic variation across a large phylogenetic range. We illustrate this approach by applying the analysis of craniofacial variation in mouse mutant models to primate and human evolution.Anthropolog

Útkoma spangar í eðlilegri fæðingu, áhrif meðferðar og stellingar á útkomu spangar

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenTilgangur þessarar rannsóknar var tvíþættur, 1. Kanna tíðni heillar spangar og tegundir rifa hjá konum sem fæddu eðlilega á Landspítala-háskólasjúkrahúsi og tíðni spangarklippinga og tengsl þeirra við rifur; 2. Kanna hvort fæðingarstelling, meðferð spangar og þyngd eða höfuðummál barns hefði áhrif á útkomu spangar. Um lýsandi framvirka rannsókn með þverskurðarsniði var að ræða. Gögnum var safnað, með skráningarlista hönnuðum af rannsakanda, frá konum sem fæddu eðlilega frá nóvember 2001 til mars 2002. Úrtakið voru 460 konur. Notuð var lýsandi tölfræði. Helstu niðurstöður: Tíðni heillar spangar var 32,5%. Tíðni 1° rifa var 30,3%, tíðni 2° rifa var 32,3% og tíðni 3° rifa var 4,4% . Alls voru 8,7% allra frumbyrja með 3° rifu og 2,2% fjölbyrja. Tíðni spangarklippinga var 8,4%. Ekki mældust skýr tengsl milli stellingar og útkomu spangar. Þrjár meðferðir höfðu áhrif á útkomu spangar. Að hvetja til rembings og að nudda/- toga spöng höfðu marktækt neikvæð áhrif. Eigið val konunnar á stellingu á öðru stigi hafði marktækt jákvæð áhrif. Ekki var marktækt samband milli fæðingarþyngdar og höfuðummáls barns og útkomu spangar

Craniofacial diversification in the domestic pigeon and the evolution of the avian skull.

A central question in evolutionary developmental biology is how highly conserved developmental systems can generate the remarkable phenotypic diversity observed among distantly related species. In part, this paradox reflects our limited knowledge about the potential for species to both respond to selection and generate novel variation. Consequently, the developmental links between small-scale microevolutionary variations within populations to larger macroevolutionary patterns among species remain unbridged. Domesticated species, such as the pigeon, are unique resources for addressing this question, because a history of strong artificial selection has significantly increased morphological diversity, offering a direct comparison of the developmental potential of a single species to broader evolutionary patterns. Here, we demonstrate that patterns of variation and covariation within and between the face and braincase in domesticated breeds of the pigeon are predictive of avian cranial evolution. These results indicate that selection on variation generated by a conserved developmental system is sufficient to explain the evolution of crania as different in shape as the albatross or eagle, parakeet or hummingbird. These 'rules' of cranio-facial variation are a common pattern in the evolution of a broad diversity of vertebrate species and may ultimately reflect structural limitations of a shared embryonic bauplan on functional variation

Morphological integration and developmental progress during fish ontogeny in two contrasting habitats

Morphological integration can respond to environmental conditions, a response that may be dynamic through ontogeny. Among fishes, brook charrs ( Salvelinus fontinalis ) display a trophic polymorphism that makes it a good species for analyzing the ontogeny of morphological integration. To better understand the processes regulating variation and integration, we assess the ontogenetic dynamics of covariances and developmental progress for populations of S. fontinalis from two habitats that differ in water velocity; lake and stream. Geometric morphometrics and developmental progress were evaluated on 751 and 198 specimens, respectively. In both habitats, most ossification events occur before the transition from alevin to juvenile. This threshold defines two distinct periods. During the first period representing free-embryos and alevins, there are important shape changes and rapid ossification, integration tends to be relatively low and decreasing and the variance of shape drastically decreases. During the juvenile period, the rate of shape change decreases and the onset of ossification is nearly complete, plus integration increases and shape variance stabilizes. While we find two distinct developmental periods, we nonetheless find a notable stability underlying the ontogenetic dynamics of variability as well as gradual change in the structure of covariation within each habitat. Our results imply that the variability of juvenile body shape does not seem to retain signals of variability determined early in ontogeny and warrants caution in using juvenile as guides to the earlier causes of variability. Overall, this study highlights the difficulty of inferring causes of integration from studies of static covariance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78677/1/j.1525-142X.2009.00381.x.pd

Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS) controls (P < 0.001). GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV) and trabecular thickness (Tb.Th), respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp.) than the GHS controls (P < 0.001). Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls) and the whole bone mechanical properties (24 to 43% larger than GHD animals) although there remained a sustained 27–52% net deficit compared to normal mice (P < 0.05). Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD