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Biomedical subjects
Publications and source records attributed to M A Ignelzi.
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The coordinate growth of the brain and skull is achieved through a series of interactions between the developing brain, the growing bones of the skull, and the fibrous joints, or sutures, that unite the bones. These interactions couple the expansion of the brain to the growth of the bony plates at the sutures. Craniosynostosis, the premature fusion of the bones of the skull, is a common birth defect (1 in 3000 live births) that disrupts coordinate growth and often results in profoundly abnormal skull shape. Individuals affected with Boston-type craniosynostosis, an autosomal dominant disorder, bear a mutated copy of MSX2, a homeobox gene thought to function in tissue interactions. Here we show that expression of the mouse counterpart of this mutant gene in the developing skulls of transgenic mice causes craniosynostosis and ectopic cranial bone. These mice provide a transgenic model of craniosynostosis as well as a point of entry into the molecular mechanisms that coordinate the growth of the brain and skull.
In this review, we provide a survey of the experimental approaches used to generate genetically engineered mice. Two specific examples are presented that demonstrate the applicability of these approaches to craniofacial development. In the first, a promoter analysis of the Msx2 gene is presented which illustrates the cis regulatory interactions that defined cell-specific gene expression. In the second, a mouse model of the human disease craniosynostosis, Boston type, has been created by misregulation of the Msx2 gene product. Finally. we present a formulary of spontaneously occurring and genetically engineered mice that exhibit defects in developmental processes affecting the craniofacial complex. The purpose of this review is to provide insight into the experimental approaches that are used to create genetically engineered mice and to impress upon the reader that genetically engineered mice are well-suited to address fundamental questions pertaining to the development maintenance, and regeneration of tissues and organs.
The nonreceptor tyrosine protein kinases pp60c-src, p59fyn, and pp62c-yes are localized in growth cones of developing neurons, but their function is undefined. To determine whether these tyrosine kinases were capable of regulating substrate-dependent axon growth, cultures of cerebellar neurons from wild-type, src-, fyn-, and yes- mice were analyzed for neurite outgrowth on the neural cell adhesion molecule L1 or the extracellular matrix protein laminin. The rate of neurite extension on L1 was reduced in src-, but not in fyn- or yes- neurons. Neurite extension on laminin was unaltered in src-, fyn-, or yes- neurons, indicating that pp60c-src, p59fyn, or pp62c-yes is not likely to participate in integrin-dependent axon growth. These results demonstrate that pp60c-src is a component of the intracellular signaling pathway in L1-mediated axonal growth and suggest that Src-related nonreceptor tyrosine kinases may have distinct, nonredundant functions in the nervous system.
The normal src protein (pp60c-src) is localized principally in the nerve growth cone of developing neurons and declines to low levels with synaptic maturation. To determine whether pp60c-src is reexpressed in regenerating axons, its expression was studied by immunoblotting and immunocytochemical analyses in adult chicken sciatic nerve following nerve crush injury. pp60c-src expression was found to increase during nerve repair with a temporal and spatial pattern consistent with a localization in regenerating axons. At the crush site, pp60c-src increased to maximal levels 7 days postinjury, increasing fivefold relative to 0 day nerve. In the nerve segment distal to the injury, the maximal increase in pp60c-src was sevenfold and occurred between 11 and 21 days postinjury. Immunoperoxidase staining revealed pp60c-src in regenerating axons and certain nonneuronal cells at the site of nerve repair. pp60c-src was induced in both motor and sensory neurons, as shown by increased pp60c-src immunoreactivity in their cell bodies located in the spinal cord and dorsal root ganglion. Phosphotyrosine-modified proteins that were potential targets of pp60c-src increased following nerve crush, and were localized to outgrowing neurites as well as to nonneuronal cells. These results suggest that pp60c-src is a common component of cellular mechanisms regulating growth cone migration in both regenerating and developing axons.
A panoramic radiograph obtained during orthodontic treatment revealed an intracoronal radiolucency within an unerupted permanent second molar. This unusual entity was successfully treated by surgical and endodontic intervention, followed by restorative and orthodontic treatment. These treatments enabled the tooth to maintain pulpal vitality, erupt, complete root formation, and function. This report will review the proposed etiologies for this condition, discuss the need for surgical intervention, and present the details of the case.
The purpose of this paper was to review the rationale for the radiographic screening of asymptomatic pediatric patients and to report the prevalence of selected pathologic and developmental conditions using panoramic radiographs. Three observers participated in this retrospective study that utilized panoramic radiographs from 849 subjects, aged 3-9 years, chosen randomly from the School of Dentistry treatment records of the University of North Carolina at Chapel Hill. Findings indicated that 2.4% of the subjects had supernumerary teeth, 7.8% were missing permanent teeth, 9.1% had ectopic eruption, 0.1% had radiolucencies of the jaws, and 0.1% had radiopacities of the jaws. These prevalences are discussed in light of recent evidence concerning the risk/benefit ratio of the panoramic radiograph. We conclude that the panoramic radiograph is a poor projection for screening the dental needs of asymptomatic healthy children; alternative screening protocols should be examined.