Akira Imamoto

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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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...

Shemon AN, Eves EM, Clark MC, Heil G, Granovsky A, Zeng L, Imamoto A, Koide S, Rosner MR. (2009) “Raf Kinase Inhibitory Protein protects cells against locostatin-mediated inhibition of migration.” PLoS One.4(6)  

Seo JH, Suenaga A, Hatakeyama M, Taiji M, Imamoto A. (2009) “Structural and functional basis of a role for CRKL in a fibroblast growth factor 8-induced feed-forward loop.” Mol Cell Biol. 29: 3076-87.  

Zeng L, Imamoto A, Rosner MR. (2008). Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target. Expert Opin Ther Targets. 12: 1275-87.  

Zhu F, Choi BY, Ma WY, Zhao Z, Zhang Y, Cho YY, Choi HS, Imamoto A, Bode AM, Dong Z. (2006) “COOH-terminal Src kinase-mediated c-Jun phosphorylation promotes c-Jun degradation and inhibits cell transformation.” Cancer Res. 66: 5729-36.  

Lee BC, Avraham S, Imamoto A, Avraham HK. (2006). “Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice.” Blood. 108: 904-7.  

Guris, D. L., Duester, G. Papaioannou, V. E., and Imamoto, A. (2006). "Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome." Dev Cell 10: 81-92.  [PubMed]

Moon, A. M., Guris, D. L., Seo, J.-H., Li, L., Talbot, A., Hammond, J., and Imamoto, A. (2006). "Crkl deficiency disrupts Fgf8 signaling in a mouse model of 22q11 deletion syndrome." Dev Cell 10: 71-80.  [PubMed]

Ballif, B. A., Arnaud, L., Arthur, W. T., Guris, D. L., Imamoto, A., and Cooper, J. A. (2004). "Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons." Curr Biol 14: 606-610.  [PubMed]

Duan, L. J., Imamoto, A., and Fong, G. H. (2004). "Dual roles of the C-terminal Src kinase (Csk) during developmental vascularization." Blood 103: 1370-1372.  [PubMed]

Li, L., Guris, D. L., Okura, M. and Imamoto, A. (2003). "Translocation of CrkL to focal adhesions mediates integrin-induced migration downstream of Src family kinases." Mol Cell Biol 23: 2883-92.  [PubMed]

Li, L., Okura, M. and Imamoto, A. (2002). "Focal adhesions require catalytic activity of Src family kinases to mediate integrin-matrix adhesion." Mol Cell Biol 22: 1203-17.   [PubMed]

Guris, D. L., Fantes, J., Tara, D., Druker, B. J. and Imamoto, A. (2001). "Mice lacking the homologue of the human 22q11.2 gene CRKL phenocopy neurocristopathies of DiGeorge syndrome." Nat Genet 27: 293-8.  [PubMed]

Thomas, S. M., Soriano, P. and Imamoto, A. (1995). "Specific and redundant roles of Src and Fyn in organizing the cytoskeleton." Nature 376: 267-71.  [PubMed]

Shemon AN, Eves EM, Clark MC, Heil G, Granovsky A, Zeng L, Imamoto A, Koide S, Rosner MR. (2009) “Raf Kinase Inhibitory Protein protects cells against locostatin-mediated inhibition of migration.” PLoS One.4(6)  

Seo JH, Suenaga A, Hatakeyama M, Taiji M, Imamoto A. (2009) “Structural and functional basis of a role for CRKL in a fibroblast growth factor 8-induced feed-forward loop.” Mol Cell Biol. 29: 3076-87.  

Zeng L, Imamoto A, Rosner MR. (2008). Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target. Expert Opin Ther Targets. 12: 1275-87.  

Zhu F, Choi BY, Ma WY, Zhao Z, Zhang Y, Cho YY, Choi HS, Imamoto A, Bode AM, Dong Z. (2006) “COOH-terminal Src kinase-mediated c-Jun phosphorylation promotes c-Jun degradation and inhibits cell transformation.” Cancer Res. 66: 5729-36.  

Lee BC, Avraham S, Imamoto A, Avraham HK. (2006). “Identification of the nonreceptor tyrosine kinase MATK/CHK as an essential regulator of immune cells using Matk/CHK-deficient mice.” Blood. 108: 904-7.