Takashi Mikawa, PhD


Our group investigates the molecular and cellular 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); 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); and d) induction of the cardiac conduction cell fate from bone marrow and embryonic stem cells.