CRANIOFACIAL AND CARDIAC DEVELOPMENT IN XENOPUS: A GENETIC APPROACH
K Mustafa
University Of North Carolina Chapel Hillcity: Chapel Hill country: United States (us)
Grant 5R01DE018825-04 from National Institute Of Dental & Craniofacial Research
Keywords: Adopted; Affect; Animal Model; Animals; base; Base Sequence; Biochemical; Biological; Biological Process; Biology; body system; Cardiac; cardiogenesis; Chemicals; Communities; Congenital Abnormality; craniofacial; Defect; Development; Disease; Ethylnitrosourea; Fertility; Generations; Genes; Genetic; Genetic Screening; genome sequencing; Genotype; Germ-Line Mutation; Goals; Health; Heart; high throughput screening; Human; human disease; in vivo; Infant; Intercalating Agents; interest; Libraries; Life; Link; Modeling; Molecular; Morbidity - disease rate; Mortality Vital Statistics; Mutagenesis; Mutagens; mutant; Mutation; novel; Pathology; Pathway interactions; Pattern; Pattern Formation; Phenotype; positional cloning; Protocols documentation; Reagent; Research; Role; Screening procedure; Signal Transduction; Structure; Syndrome; Tadpoles; Tissue Sample; Tissues; tool; Xenopus
Project start date: 2008-12-01
Project end date: 2013-11-30
Budget start date: 1-DEC-2011
Budget end date: 30-NOV-2012
5R01DE018825-04 (2012): $411546
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Grants awarded to K Mustafa
CHARACTERIZATION AND CLONING OF X. TROPICALIS CRANIOFACIAL MUTANTS
K Mustafa, Assistant Professor
Yale Universitycity: New Haven country: United States (us)
Grant 5R01DE018824-04 from National Institute Of Dental & Craniofacial Research
Abstract: Craniofacial malformations are among the most common birth defects in children and lead to substantial morbidity and mortality for these infants. Despite the severity of the illness, little is known about the molecular mechanisms that are necessary for correct formation of facial structures. In this proposal, we will investigate craniofacial development in an emerging model system, Xenopus tropicalis. During a recent forward genetic screen, we identified two mutants, jaws and jawbreaker, that exhibit a specific embryonic defect in the development of craniofacial structures. These mutants show a simple Mendelian inheritance pattern suggestive of a single recessive mutant locus. Outside of the craniofacial defect, the remainder of the embryo appears wildtype. It is the goal of this proposal to characterize these two mutants and identify where and when during development craniofacial patterning begins to fail. In a second aim, we will attempt to identify the mutant locus which will greatly improve our understanding of the molecular patterning defect. Because our understanding of craniofacial morphogenesis remains superficial, characterizing these mutants has the potential of substantially improving our understanding of craniofacial development and malformations. In addition, this will represent one of the very first attempts to clone a mutant identified in a forward genetic screen in X. tropicalis. Successful completion of these goals will greatly support future genetic screens in this emerging model system. Birth defects of the head and neck are a common cause of serious illness in infants. Yet, our scientific understanding of how these structures form during embryonic development remains superficial. We propose a series of experiments to analyze two frog mutants that have abnormal jaw structure. A better understanding of these frog mutants can then be used as a model to understand birth defects of the head and neck in humans
Keywords: Affect; base; Biological Models; Branchial arch structure; Candidate Disease Gene; Cell Death; Cell division; Child; Childhood; Cloning; comparative; Congenital Abnormality; cost effective; craniofacial; Data; Defect; Development; Disease; Embryo; Embryonic Development; Endothelin; Evolution; Exhibits; Face; Funding; Future; gene function; Genes; Genetic; genetic analysis; Genetic Models; Genetic Screening; Genomics; Glean; Goals; Grant; Head; Head and neck structure; Health; Human; human disease; Hybrids; improved; Infant; Infant Mortality; Inheritance Patterns; Inherited; insight; Jaw; knock-down; Lead; Learning; malformation; Messenger RNA; migration; Modeling; Molecular; Morbidity - disease rate; Morphogenesis; Mus; mutant; Mutate; Mutation; Neural Crest; Neural Crest Cell; novel; Oligonucleotides; Pathway interactions; Pattern; Phenocopy; Phenotype; positional cloning; programs; Proteins; Rana (genus); Recombinants; Research Personnel; research study; Series; Severity of illness; Signal Transduction; skeletal; Staging; Structure; System; Testing; Tissues; Transcript; Ursidae Family; Xenopus; Yaws
Project start date: 2008-08-01
Project end date: 2013-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: PAR-05-166
5R01DE018824-04 (2011): $311502