Biomedical subjects

Haruki Ochi

Publications and source records attributed to Haruki Ochi.

4 recordsLinked to original sources

PubMed2007

Signaling networks that regulate muscle development: lessons from zebrafish.

Locomotion mediated by skeletal muscle provides a basis for the behavioral repertoire of most animals. Embryological and genetic studies of mouse, bird, fish and frog embryos are providing insights into the functions of the myogenic regulatory factors (MRFs) and the signaling molecules that regulate activity of MRFs. Nevertheless, our understanding of muscle development remains somewhat limited. Fundamental goals are to elucidate how mesodermal cells are induced during gastrulation to form muscle precursor cells and how muscle precursor cells acquire specific cell fates, such as slow and fast muscle cells. In this review, we focus on studies of zebrafish muscle development that have advanced our understanding of the molecular genetics of muscle cell induction and specification.

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PubMed2006

Hhip regulates zebrafish muscle development by both sequestering Hedgehog and modulating localization of Smoothened.

Sharp borders between cells with different developmental fates are important for patterning of invertebrates, but are not well understood in vertebrates. Zebrafish slow muscle cells develop from adaxial cells, a one-cell-diameter-thick pseudo-epithelium immediately adjacent to the notochord. Hedgehog (Hh) signals from notochord specify adaxial cells to form slow muscle cells. Cells next to adaxial cells form fast muscle. This suggests that Hh signaling is locally regulated to produce a sharp border that separates slow and fast muscle precursors. To understand how Hh activity is locally regulated, we characterized the dynamic roles of Hhip, a protein that binds Hedgehog at the cell surface. Hhip is strongly expressed by adaxial cells and, together with Patched, the Hedgehog receptor, limits transduction of the Hedgehog signaling by Smoothened to adaxial cells. Hhip protein lacking its membrane associated domain still suppresses Hh activity but no longer acts synergistically with Patched. Hhip and Smoothened colocalize at the cell surface and, in response to Hedgehog, internalize together. Knockdown of Hhip blocks Smoothened internalization while increasing Hedgehog signaling and slow muscle formation. These data support a model in which Hhip regulates muscle development both by sequestering Hedgehog and by modulating localization of Smoothened.

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PubMed2004

Temporal expression of L-Maf and RaxL in developing chicken retina are arranged into mosaic pattern.

Members of the maf gene family encode basic/leucine zipper transcription factors and play important roles during cell differentiation in vertebrate and Drosophila development. To investigate the possible roles of chicken lens-specific Maf (L-Maf)/MafA in retinal development, we analyzed its expression in the developing chicken retina. We first determined that L-Maf is expressed in a subset of ganglion cells, amacrine cells and rod cells during retinal development. To characterize further the L-Maf expressing cells during photoreceptor development, we compared the expression patterns of L-Maf and RaxL, a marker of cone cells. We found the L-Maf proteins are detectable from E10 between RaxL positive cone cells in outer nuclear layer (ONL). Subsequently, the expression of L-Maf is restricted to the innermost nuclear cells in the ONL during rod differentiation. In contrast, RaxL positive cone cells are distributed in the outermost layer of ONL. Furthermore, tangential retinal sections showed that L-Maf positive rods and RaxL positive cones form a mosaic pattern during photoreceptor development.

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PubMed2002

The stability of the lens-specific Maf protein is regulated by fibroblast growth factor (FGF)/ERK signaling in lens fiber differentiation.

Fibroblast growth factor (FGF) signaling is necessary for both proliferation and differentiation of lens cells. However, the molecular mechanisms by which FGFs exert their effects on the lens remain poorly understood. In this study, we show that FGF-2 repressed the expression of lens-specific genes at the proliferative phase in primary cultured lens cells. Using transfected cells, we also found that the activity of L-Maf, a lens differentiation factor, is repressed by FGF/ERK signaling. L-Maf is shown to be phosphorylated by ERK, and introduction of mutations into the ERK target sites on L-Maf promotes its stabilization. The stable L-Maf mutant protein promotes the differentiation of lens cells from neural retina cells. Taken together, these results indicate that FGF/ERK signaling negatively regulates the function of L-Maf in proliferative lens cells and that stabilization of the L-Maf protein is important for lens fiber differentiation.

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