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Takashi Mikawa, PhD
Developmental Regulation of Organogenesis


Our group investigates the molecular mechanisms involved in the differentiation and patterning of the cardiovascular and central nervous systems. Both organ systems share a common developmental plan to establish their extremely complicated structures and functions: i) construction of a tubular structure from an epithelial sheet along midline body axis, ii) subdivision of the epithelial tube into zones for distinct functional components of the organ, iii) proliferation of cells along a perpendicular axis to the epithelial sheet (clone unit), and iv) cell fate diversification within clone units. Thus, growth of both organs is characterized by the daughter cells from the epithelial sheets proliferating vertically while remaining in close association, thereby generating clone arrays. Three dimensional spherical structures of both the heart and brain are established by the lateral packing of clone units. These findings indicate that each clone is a primary unit for both differentiation and morphogenesis of these organ systems. We are currently analyzing the molecular basis of several of these processes including a) formation of a tubular organ primordium; establishment of the midline identity along which a tubular primordium forms; b) subdivision of neural and non-neural zones during development of the retina (an extension of neural tube); and c) diversification within clone units into the glial and neuronal cell fate (neural retina, optic tectum) and the conversion of myocytes to the impulse conducting cell linage (heart).

Selected Publications

Mima T, Ueno H, Fischman DA, Williams LT, Mikawa T. Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development. Proc Natl Acad Sci U S A. 1995 92:467-471.

Hyer J, Mima T, Mikawa T. FGF1 patterns the optic vesicle by directing the placement of the neural retina domain. Development. 1998 125:869-877

Wei Y, Mikawa T. Formation of the avian primitive streak from spatially restricted blastoderm: evidence for polarized cell division in the elongating streak. Development. 2000 127:87-96.

Reese DE, Hall CE, Mikawa T. Negative regulation of midline vascular development by the notochord. Dev Cell. 2004 6:699-708.

Mima T, Mikawa T. Folding of the tectal cortex by local remodeling of neural differentiation. Dev Dyn. 2004 229:475-479.

Hall CE, Hurtado R, Hewett KW, Shulimovich M, Poma CP, Reckova M, Justus C, Pennisi DJ, Tobita K, Sedmera D, Gourdie RG, Mikawa T. Hemodynamic-dependent patterning of endothelin converting enzyme 1 expression and differentiation of impulse-conducting Purkinje fibers in the embryonic heart. Development. 2004 131:581-592.

Ishii Y, Mikawa T. Somatic transgenesis in the avian model system. Embryo Today. 2005 75:19-27.


information last updated June 2006



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