Abstract
Development of the pharyngeal region depends on the interaction and integration of different cell populations, including surface ectoderm, foregut endoderm, paraxial mesoderm, and neural crest. Mice homozygous for a hypomorphic allele of Fgfr1 have craniofacial defects, some of which appeared to result from a failure in the early development of the second branchial arch. A stream of neural crest cells was found to originate from the rhombomere 4 region and migrate toward the second branchial arch in the mutants. Neural crest cells mostly failed to enter the second arch, however, but accumulated in a region proximal to it. Both rescue of the hypomorphic Fgfr1 allele and inactivation of a conditional Fgfr1 allele specifically in neural crest cells indicated that Fgfr1 regulates the entry of neural crest cells into the second branchial arch non-cell-autonomously. Gene expression in the pharyngeal ectoderm overlying the developing second branchial arch was affected in the hypomorphic Fgfr1 mutants at a stage prior to neural crest entry. Our results indicate that Fgfr1 patterns the pharyngeal region to create a permissive environment for neural crest cell migration.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Animals
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Apoptosis
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Branchial Region / pathology
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Cell Movement
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Cleft Palate / embryology
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Cleft Palate / genetics
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Craniofacial Abnormalities / embryology
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Craniofacial Abnormalities / genetics
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Ear, Middle / abnormalities
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Ear, Middle / embryology
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Ectoderm / metabolism
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Epithelium / embryology
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Gene Expression Regulation, Developmental
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Genes, Lethal
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Hyoid Bone / abnormalities
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Hyoid Bone / embryology
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Integrases / genetics
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Integrases / physiology
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Mice
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Morphogenesis / genetics
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Neural Crest / cytology*
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Pharynx / embryology*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology
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Receptor Protein-Tyrosine Kinases / physiology*
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Receptor, Fibroblast Growth Factor, Type 1
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Receptors, Fibroblast Growth Factor / physiology*
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Recombinant Fusion Proteins / physiology
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Rhombencephalon / abnormalities
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Rhombencephalon / embryology
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Viral Proteins / genetics
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Viral Proteins / physiology
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Wnt Proteins
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Zebrafish Proteins*
Substances
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Proto-Oncogene Proteins
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Receptors, Fibroblast Growth Factor
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Recombinant Fusion Proteins
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Viral Proteins
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Wnt Proteins
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Zebrafish Proteins
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Fgfr1 protein, mouse
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 1
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Cre recombinase
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Integrases