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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.07.016 Byline: B. McBratney-Owen (a), S. Iseki (b), S.D. Bamforth (c), B.R. Olsen (a), G.M. Morriss-Kay (d) Keywords: Cranial base; Chondrocranium; Neural crest; Mesoderm; Wnt1; Mesp1; New Head Hypothesis; Tissue origins; Cranial development Abbreviations: A, ala temporalis cartilage; AC, auditory capsule; ACO, alicochlear commissure; AR, acrochordal cartilage; AT, ala temporalis (greater wing) of basisphenoid bone; B, basitrabecular process; BF, basicranial fenestra; BO, basioccipital bone; BS, basisphenoid bone; CA, canalicular part of auditory capsule; CM, cranial mesenchyme; CO, cochlear part of auditory capsule; DI, diencephalon; EB, ethmoid bone; EO, exoccipital bone (will eventually fuse to basioccipital bone); F, frontal cartilage; FB, frontal bone; FV, fourth ventricle of hindbrain; GW, greater wing (ala temporalis) of the basisphenoid bone; H, hypophyseal cartilage; HF, hypophyseal fenestra; LW, lesser wing of the presphenoid bone; MNP, medial nasal process; MV, mesencephalic vesicle of midbrain; MX, maxillary process; NL, orbitonasal lamina of the paranasal cartilage; O, orbital cartilage; OA, occipital arch cartilage; OF, optic foramen; ON, optic nerve; OR, optic recess; P, parachordal cartilage; PA, parietal cartilage; PI, developing pituitary gland; PN, paranasal cartilage; PS, presphenoid bone; PSS, presphenoidal synchondrosis; S, supraoccipital cartilage; SB, supraoccipital bone (will eventually fuse to basioccipital bone); SOS, spheno-occipital synchondrosis; SQ, squamosal bone; T, trabecular cartilage (trabecular plate); TB, basal portion of trabecular plate; TG, trigeminal nerve; TN, nasal portion of trabecular plate; To, Tongue; TV, third ventricle of forebrain; Y, hypochiasmatic cartilage Abstract: The vertebrate cranial base is a complex structure composed of bone, cartilage and other connective tissues underlying the brain; it is intimately connected with development of the face and cranial vault. Despite its central importance in craniofacial development, morphogenesis and tissue origins of the cranial base have not been studied in detail in the mouse, an important model organism. We describe here the location and time of appearance of the cartilages of the chondrocranium. We also examine the tissue origins of the mouse cranial base using a neural crest cell lineage cell marker, Wnt1-Cre/R26R, and a mesoderm lineage cell marker, Mesp1-Cre/R26R. The chondrocranium develops between E11 and E16 in the mouse, beginning with development of the caudal (occipital) chondrocranium, followed by chondrogenesis rostrally to form the nasal capsule, and finally fusion of these two parts via the midline central stem and the lateral struts of the vault cartilages. X-Gal staining of transgenic mice from E8.0 to 10 days post-natal showed that neural crest cells contribute to all of the cartilages that form the ethmoid, presphenoid, and basisphenoid bones with the exception of the hypochiasmatic cartilages. The basioccipital bone and non-squamous parts of the temporal bones are mesoderm derived. Therefore the prechordal head is mostly composed of neural crest-derived tissues, as predicted by the New Head Hypothesis. However, the anterior location of the mesoderm-derived hypochiasmatic cartilages, which are closely linked with the extra-ocular muscles, suggests that some tissues associated with the visual apparatus may have evolved independently of the rest of the 'New Head'. Author Affiliation: (a) Harvard School of Dental Medicine, Department of Developmental Biology, 190 Longwood Avenue, Boston, MA, 02115, USA (b) Molecular Craniofacial Embryology Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan (c) Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, OX3 7BN, UK (d) Le Gros Clark Building, Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford, OX1 3QX, UK Article History: Received 24 January 2008; Revised 10 July 2008; Accepted 10 July 2008

High-mobility group box-1 (HMGB1) protein acts as a transcription factor in the nucleus and also as a pro-inflammatory cytokine when released into extracellular fluids. The presence of higher levels of HMGB1 is reported in the gingival crevicular fluid from periodontal patients. Since the proliferation of bacteria within the periodontal pocket is closely involved in the exacerbation of periodontal disease, it is hypothesized that the periodontal pocket causes the release of HMGB1. Immunohistochemical staining of inflamed gingiva revealed that HMGB1 is exclusively dislocated from the nucleus to the cytoplasm in the pocket epithelium, whereas it is mainly present in the nucleus in the gingival epithelium. Butyric acid, an extracellular metabolite from periodontopathic bacteria populating the periodontal pocket, induced the passive release of HMGB1 as a result of eliciting necrosis in the human gingival epithelial cell line. Thus, the periodontal epithelium may provide a unique pathological setting for HMGB1 release by bacterial insult. Abbreviations: HMGB1, high-mobility group box-1; TNF-α, tumor necrosis factor-α; CHX, cycloheximide; PI, propidium iodide; ROS, reactive oxygen species; HDAC, histone deacetylase. [ABSTRACT FROM PUBLISHER]