DDS, Osaka University, Osaka, Japan
PhD, Osaka University, Osaka, Japan
Postdoctoral Fellowship, Fred Hutchinson Cancer Research Center, Seattle, WA
Our laboratory is interested in elucidating fundamental mechanisms of mammalian development during morphogenesis and fate determination. We currently focus on elucidating the molecular and developmental etiology of a human syndrome called DiGeorge/velocardiofacial syndrome (OMIM: 188400 and 192430), the most frequent deletion syndrome affecting approximately 1 in 4000 live births. The common manifestations of this syndrome include cardiovascular defects, aplasia or hypoplasia of the thymus and parathyroid glands, and craniofacial anomalies. Urogenital defects, learning disabilities, and other psychiatric disorders are also common. The molecular basis of DGS comprises heterozygous deletions at 22q11.21 likely mediated by recombination between chromosome 22-specific low copy repeats scattered around this region. The most common deletion encompasses 3 Mb in approximately 90% of the patients. DGS candidate genes, including TBX1 and CRKL, have been mapped within this region.
Using techniques available in mouse genetics and developmental biology we investigate the relationship betweenCRKL and TBX1 as well as other 22q11 genes during the process that determines correct anterior-posterior identities of the pharyngeal apparatus. In addition, our results suggest that CRKL is required for cell survival, patterning, and fate determination. We are testing this hypothesis in order to understand the biology of pharyngeal arch development which is coordinated by interaction between the endoderm, ectoderm, mesoderm, and neural crest-derived mesenchyme.
We also ask other fundamental questions in cell and developmental biology concerning inter- and intracellular signaling that influences decision making processes of cell behavior and fate.
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