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" Early and late steps in Craniofacial Development: A survey of Neural Crest, Muscle progenitors and the fine-tuning between them "
Ariel Rinon
E. Tzahor
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Latin Dissertation
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English
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| Record Number
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54141
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TL24095
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3510119
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| Main Entry
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Ariel Rinon
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| Title & Author
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Early and late steps in Craniofacial Development: A survey of Neural Crest, Muscle progenitors and the fine-tuning between them\ Ariel Rinon
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| College
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The Weizmann Institute of Science (Israel)
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| Date
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2009
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Ph.D.
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2009
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83
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| Abstract
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In the vertebrate head, mesoderm cells fuse together to form a myofiber, which is attached to specific cranial neural crest (CNC)-derived skeletal element in a highly coordinated manner. The interactions between these populations during early development remain controversial. In this work we explored the nature of the crosstalk between CNC and mesoderm cells during head muscle development employing three models for genetic perturbations of CNC development in mice, as well as experimental ablation of CNC in chick embryos. We demonstrated that although early myogenesis is CNC-independent, the migration, patterning and differentiation of muscle precursors are regulated by CNC. In the absence of CNC cells, accumulated myoblasts are kept at a proliferative state, presumably due to an increase of Fgf8 in adjacent tissues, which lead to abnormal differentiation and subsequent myofiber organization in the head. These findings were published in Development (Rinon et al., 2007). The molecular underpinnings of this crosstalk are still poorly understood. To this end we studied the role of the tumor suppressor gene, p53 in craniofacial development. p53 has been implicated in many cellular activities, although loss-of-function studies revealed that p53 is dispensable for embryonic development. We first noticed that p53 is expressed exclusively in non-muscles tissues (e.g., CNC and ectoderm). To further investigate the role of this gene in CNC and head muscles development, we utilized the chick system for both gain and loss of function experiments and p53 knockout in the mouse. In the chick, we applied a pharmacological inhibitor of MDM2 (p53's negative regulator) and used the electroporation system to missexpress the wild type (wt) p53 version in the CNC. Increased levels of p53 reduced Snail2 (formerly known as Slug) expression, apparently leading to fewer migrating CNC cells from the neural tube. Loss of p53 activity by missexpression of MDM2 or DNp53, a dominant negative form of p53, in these cells increased the expression of Pax7, Sox9 and later Snail2, presumably augmenting CNC delamination. Analysis of the mouse model revealed that in some p53 embryos, defects in cranial skeleton (bones and cartilage) exist. Moreover p53 mutants exhibit some patterning defects of the extraocular muscles (EOM) and mastication muscles. Our collective findings suggest an essential regulatory role for p53 at different developmental stages of CNC and a non cell-autonomous role for this population on the adjacent skeletal muscle progenitors
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Biological sciences; Cranial neural crest; Mesoderm cells; Muscle progenitors; Myofibers; Biology; Neurosciences; Cellular biology; 0306:Biology; 0379:Cellular biology; 0317:Neurosciences
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E. Tzahor
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The Weizmann Institute of Science (Israel)
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