Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone. Parietal and frontal bones are formed by intramembranous ossification within a layer of mesenchyme positioned between the dermal mesenchyme and meninges surrounding the brain. The supraoccipital bone has an endochondral origin. Cranial bones are separated by connective tissue with a distinctive architecture of osteogenic cells and collagen fibrils. Here we show RNA in situ hybridization for col1a1a, col2a1a, col10a1, bglap/osteocalcin, fgfr1a, fgfr1b, fgfr2, fgfr3, foxq1, twist2, twist3, runx2a, runx2b, sp7/osterix, and spp1/ osteopontin, indicating that the expression of genes involved in suture development in mammals is preserved in zebrafish. We also present methods for examining the cranium and its sutures, which permit the study of the mechanisms involved in suture patency as well as their pathological obliteration. The model we develop has implications for the study of human disorders, including craniosynostosis, which affects 1 in 2,500 live births.

nox-4 activity resulted in decreased hydrogen peroxide production and decreased production of oxidant inducible monocyte chemoattractant protein-1. ConClusions:These are the first reported results to demonstrate the significant contribution of dicer activity and miR production in promoting hemangioendothelioma growth in vivo. These are also the first reported results of miR21a-3p targeting nox-4 mRNA and inhibiting reactive oxygen species production in endothelial cells. Collectively, these results indicate that targeting microRNA and specifically, miR-21a-3p, represent potential therapeutic strategies for the treatment of endothelial cell tumors including hemangioma and hemangioendothelioma.

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PurPose: Studies from NYU revealed that following nasoalveolar molding/gingivoperiosteoplasty (GPP) 60% of patients did not require an alveolar bone graft. In our lab midface animal growth was not detrimentally affected after BMP-2 healing of alveolar clefts. In this study, we performed a similar procedure to NYU with alveolar molding/GPP but with BMP-2 on a resorbable matrix for primary alveolar repair in the infant. We compared long-term follow-up (10 years) for 1) No GPP, 2) GPP only or 2) GPP with BMP-2 by analyzing alveolar bone, tooth eruption, and maxillary growth. Methods:For the three primary unilateral cleft repair patient groups: 1) No GPP (n=15), 2) GPP only (n=15) or 2) GPP with BMP-2 (n=10) we performed follow-up studies at least 10 years after the procedure. There was one GPP patient lost to follow-up. We recorded need for secondary alveolar bone grafting, timing of tooth eruption, and clinical evidence of maxillary hypoplasia. New-Tom scans were used to analyze dentition, bone volume and bone density.