Soluble form of FGFR2 with S252W partially prevents craniosynostosis of the apert mouse model

Background: Apert syndrome (AS) is characterized by craniosynostosis, midfacial hypoplasia, and bony syndactyly. It is an autosomal dominantly inherited disease caused by point mutations (S252W or P253R) in fibroblast growth factor receptor (FGFR) 2. These mutations cause activation of FGFR2 depending on ligand binding. Recently, an AS mouse model, Fgfr2^+/S252W, showed phenotypes similar to those of AS patients. We previously reported that the soluble form of FGFR2^S252W (sFGFR2IIIc^S252W) efficiently inhibits enhanced osteoblastic differentiation caused by FGFR2 activation in AS in vitro, presumably because FGFs binding to FGFRs is interrupted. In this study, we developed Fgfr2^+/S252W (Ap) mice expressing the sFGFR2IIIc^S252W protein, and we investigated the effects of sFGFR2IIIc^S252W on AS‐like phenotypes. Results: In Ap mice, the coronal suture (CS) was fused prematurely at P1. In addition, the mice exhibited a widened interfrontal suture (IFS) with ectopic bone and thickened cartilage formation. In Fgfr2^+/S252W sFGFR2IIIc^S252W (Ap/Sol) mice, the CS was similar to that of wild‐type mice. Ap/Sol mice did not show any ectopic bone or cartilage formation in the IFS, but showed a wider IFS than that of the wild‐type mice. Conclusions: sFGFR2IIIc^S252W may partially prevent craniosynostosis in the Apert mouse model by affecting the CS and IFS in vivo. Developmental Dynamics 243:560–567, 2014. © 2013 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.     

The insular auditory field receives input from the lemniscal subdivision of the auditory thalamus in mice

The insular cortex plays important roles in vocal communication, but the origin of auditory input to the insular cortex has not been fully clarified. Here we studied the auditory thalamic input to the insular cortex using mice as a model system. An insular auditory field (IAF) has recently been identified in mice. By using retrograde neuronal tracing, we identified auditory thalamic neurons projecting to the IAF, primary auditory cortex (AI), and anterior auditory field (AAF). After mapping the IAF, AAF, and AI by using optical imaging, we injected a distinct fluorescent tracer into each of the three fields at frequency‐matched locations. Tracer injection into the IAF resulted in retrogradely labeled cells localized ventromedially in the lemniscal division, i.e., the ventral subdivision of the medial geniculate body (MGv). Cells retrogradely labeled by injections into the AAF were primarily found in the medial half of the MGv, whereas those from AI injections were located in the lateral half, although some of these two subsets were intermingled within the MGv. Interestingly, retrogradely labeled cells projecting to the IAF showed virtually no overlap with those projecting to the AAF or the AI. Dual tracer injections into two sites responding to low‐ and high‐frequency tones within each of the three auditory fields demonstrated topographic organizations in all three thalamocortical projections. These results indicate that the IAF receives thalamic input from the MGv in a topographic manner, and that the MGv–IAF projection is parallel to the MGv–AAF and MGv–AI projections. J. Comp. Neurol. 522:1373–1389, 2014. © 2013 Wiley Periodicals, Inc.     

Histopathological correlates of the napkin-ring sign plaque in coronary CT angiography

ObjectiveThe purpose of this study was to identify histologic characteristics of advanced coronary atherosclerotic plaques that are related with the detection of the napkin-ring sign (NRS) in coronary CT angiography (CCTA).MethodsCCTA was performed in 7 human donor hearts. Histological slicing and stainings were performed in 1 mm increments of each major coronary artery. Histology was co-registered with the CT-data and classified according to the modified AHA classification.ResultsAdvanced plaques (types IV–VI) were present in 139 (23%) of 611 cross sections. Of these 33 (24%) demonstrated an NRS in CCTA. NRS plaques were associated with greater non-core plaque area (median 10.2 vs. 6.4 mm², p < 0.01) and larger vessel area (median 17.1 vs. 13.0 mm², p < 0.01). The area of the necrotic/lipid core was larger in plaques with NRS (median 1.1 vs. 0.5 mm², p = 0.05). Angiogenesis tended to be more frequent in plaques with NRS (48% vs. 30%) whereas micro-calcifications tended to be more frequent in plaques without NRS (27% vs. 46%) (p = 0.06 and 0.07 respectively). In a multivariate analysis, necrotic/lipid core area (OR = 1.9), non-core plaque area (OR = 1.6), and total vessel area (OR = 0.9) independently predicted the appearance of the NRS in coronary CT angiography.ConclusionDelineation of NRS in CCTA is independently linked to the size of the necrotic/lipid core, the size of the non-core plaque and to the vessel area as measured in histology of advanced coronary atherosclerotic plaques.     

Distributions of calcitonin gene-related peptide and substance P in the human maxillary sinus of Japanese cadavers

BackgroundSubstance P (SP) and calcitonin gene-related peptide (CGRP) are released by the nociceptive sensory nerve and are involved in blood flow, pain and inflammation in the nasal mucosa. The purpose of this study was to assess the distribution of the SP and CGRP nerve fibres related to blood supply within human Schneiderian membrane of the maxillary sinus (MS).Material and methodsIn this study, the MS from Japanese cadavers was examined by whole-mount immunohistochemistry. Human male cadavers (ranging in age from 80 to 90 years) were used in this study.ResultsSP- and CGRP-positive fibres were found around large vessels of the medialis superior alveolar branches and also within the floor region of the MS. The floor region of the MS was composed of complex branches of these fibres.ConclusionOur results give useful information for surgical sinus floor elevation in this region of the MS. These anatomical features may assist in the execution of a successful surgical procedure.