Computerised 3-D anatomical modelling using plastinates: an example utilising the human heart

Computerised modelling methods have become highly useful for generating electronic representations of anatomical structures. These methods rely on crosssectional tissue slices in databases such as the Visible Human Male and Female, the Visible Korean Human, and the Visible Chinese Human. However, these databases are time consuming to generate and require labour-intensive manual digitisation while the number of specimens is very limited. Plastinated anatomical material could provide a possible alternative to data collection, requiring less time to prepare and enabling the use of virtually any anatomical or pathological structure routinely obtained in a gross anatomy laboratory. The purpose of this study was to establish an approach utilising plastinated anatomical material, specifically human hearts, for the purpose computerised 3-D modelling. Human hearts were collected following gross anatomical dissection and subjected to routine plastination procedures including dehydration (–25oC), defatting, forced impregnation, and curing at room temperature. A graphics pipeline was established comprising data collection with a hand-held scanner, 3-D modelling, model polishing, file conversion, and final rendering. Representative models were viewed and qualitatively assessed for accuracy and detail. The results showed that the heart model provided detailed surface information necessary for gross anatomical instructional purposes. Rendering tools facilitated optional model manipulation for further structural clarification if selected by the user. The use of plastinated material for generating 3-D computerised models has distinct advantages compared to cross-sectional tissue images. (Folia Morphol 2011; 70, 3: 191–196

Canalization and developmental stability in the Brachyrrhine mouse

The semi-dominant Br mutation affects presphenoid growth, producing the facial retrognathism and globular neurocranial vault that characterize heterozygotes. We analysed the impact of this mutation on skull shape, comparing heterozygotes to wildtype mice, to determine if the effects are skull-wide or confined to the sphenoid region targeted by the mutation. In addition, we examined patterns of variability of shape for the skull as a whole and for three regions (basicranium, face and neurocranium). We found that the Br mice differed significantly from wildtype mice in skull shape in all three regions as well as in the shape of the skull as a whole. However, the significant increases in variance and fluctuating asymmetry were found only in the basicranium of mutant mice. These results suggest that the mutation has a significant effect on the underlying developmental architecture of the skull, which produces an increase in phenotypic variability that is localized to the anatomical region in which the mean phenotype is most dramatically affected. These results suggest that the same developmental mechanisms that produce the change in phenotypic mean also produce the change in variance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75710/1/j.1469-7580.2006.00527.x.pd

Morphometry of the Cranial Base in Subjects with Class III Malocclusion

The significance of the cranial base in the development of Class III malocclusion remains uncertain. The purpose of this study was to determine whether the form of the cranial base differs between prepubertal Class I and Class III subjects. Lateral cephalographs of 73 children of European-American descent aged between 5 and 11 years with Class III malocclusion were compared with those of their counterparts with a normal, Class I molar occlusion. The cephalographs were traced, checked, and subdivided into seven age- and sex-matched groups. Average geometries, scaled to an equivalent size, were generated based on 13 craniofacial landmarks by means of Procrustes analysis, and these configurations were statistically tested for equivalence. Bivariate and multivariate analyses utilizing 5 linear and angular measurements were undertaken to corroborate the Procrustes analysis. Graphical analysis, utilizing thin-plate spline and finite element methods, was performed for localization of differences in cranial base morphology. Results indicated that cranial base morphology differed statistically for all age-wise comparisons. Graphical analysis revealed that the greatest differences in morphology occurred in the posterior cranial base region, which generally consisted of horizontal compression, vertical expansion, and size contraction. The sphenoidal region displayed expansion, while the anterior regions showed shearing and local increases in size. It is concluded that the shape of the cranial base differs in subjects with Class III malocclusion compared with the normal Class I configuration, due in part to deficient orthocephalization, or failure of the cranial base to flatten during development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67377/2/10.1177_00220345970760021101.pd

Spatial and temporal dynamics of innervation during the development of fetal human pancreas.

The delineation of pancreatic nerve innervations during fetal life may contribute to our understanding of pancreatic pain modalities after birth. The aim of this study was to characterize the spatial and temporal distribution of nerve structures in the human pancreas throughout gestation. Computer-based image morphometry with piecewise polynomial interpolation analysis was performed to quantify nervous structures in the head, body and tail of the pancreas. Nerve structures were detected by automatic immunostaining techniques using a polyclonal antibody against two S-100 proteins that reacts strongly with human S100A and B that are detected in Schwann cells. Immunoreactivity was found in the parenchyma of head, body and tail of the pancreas with the relative density being head> body> tail. In addition to this extensive set of nerve fibers terminating in the pancreas there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that were 3D reconstructed and were associated with the superior mesenteric plexus. If at first glance, the perimeter and the width of the nerve fibers seem to increase at a continuous rate up to term in all three regions of the pancreas, spatial and temporal co-analysis identified that the head of the pancreas shows a two-peak growth increase at 14 and 22 weeks of gestation with regard to the area, perimeter and width of the nerve structures, while the body and tail regions show a unique peak at 20 weeks. A developmental deceleration was found between the 22nd and the 36th week of gestation for the head region only. This is the first systematic study of nerve innervation of the human pancreas throughout gestation. The developmental dynamics of the pancreas nerve innervation corresponds approximately to the remodeling of the intrahepatic biliary system. Understanding the factors and disease states that may alter the distribution of nerve structures can be of significance for the development of therapies in pancreatic disorders of child- and adulthood

A mutation in the tuft mouse disrupts TET1 activity and alters the expression of genes that are crucial for neural tube closure

Genetic variations affecting neural tube closure along the head result in malformations of the face and brain. Neural tube defects (NTDs) are among the most common birth defects in humans. We previously reported a mouse mutant called tuft that arose spontaneously in our wild-type 3H1 colony. Adult tuft mice present midline craniofacial malformations with or without an anterior cephalocele. In addition, affected embryos presented neural tube closure defects resulting in insufficient closure of the anterior neuropore or exencephaly. Here, through whole-genome sequencing, we identified a nonsense mutation in the Tet1 gene, which encodes a methylcytosine dioxygenase (TET1), co-segregating with the tuft phenotype. This mutation resulted in premature termination that disrupts the catalytic domain that is involved in the demethylation of cytosine. We detected a significant loss of TET enzyme activity in the heads of tuft embryos that were homozygous for the mutation and had NTDs. RNA-Seq transcriptome analysis indicated that multiple gene pathways associated with neural tube closure were dysregulated in tuft embryo heads. Among them, the expressions of Cecr2, Epha7 and Grhl2 were significantly reduced in some embryos presenting neural tube closure defects, whereas one or more components of the non-canonical WNT signaling pathway mediating planar cell polarity and convergent extension were affected in others. We further show that the recombinant mutant TET1 protein was capable of entering the nucleus and affected the expression of endogenous Grhl2 in IMCD-3 (inner medullary collecting duct) cells. These results indicate that TET1 is an epigenetic determinant for regulating genes that are crucial to closure of the anterior neural tube and its mutation has implications to craniofacial development, as presented by the tuft mouse