YOSHIZATO MorphoMatrix

yoshizato_portrait

Animals show a quite interesting phenomenon called reconstitution, even after establishing their body structure through embryogenesis. A frog drastically changes its shape from a larva to oan adult(transformation or metamorphosis). and a newt completely reproduces its missing limb(regeneration). A major theme of this project was to elucidate the mechanisms of transformation and regeneration. The skin and liver of mammals were also targets of investigations, because of their exceptional regenerative potential in the mammalian body. For understanding the molecular mechanisms underlying these processes, the expressions of morphogenesis-associated genes as well as the roll of extracellular matrices as structural information molecules were investigated. The isolation and characterization of tissue progenitor-like cells were also important for understanding the mechanism and useful for reconstituting the dimensional artificial tissues and organs.

Research Director: Dr.Katsutoshi Yoshizato
(Professor Faculty of Science Hiroshima University)
Research Term 1992~1997

 

Research result

Genes associated with transformation:

 A total of thirteen transformation-associated genes were isolated from Xenopus, including seven unknown and six known genes.

Genes associated with limb regeneration:

 It was revealed that the expression of four matrix metalloproteinases and sonic hedgehog genes are closely related to the reconstitution process of amputated limbs. Two novel genes were isolated, which were found to be distinctly expressed in regenerating tissues.

Progenitor cells in the liver:

 Small hepatocytes were successfully isolated and cultivated as progenitor cells of the liver. The cells had a bipotency, and differentiated into both matured hepatocytes and bile-duct cells.

Pleiotrophin as a novel potent growth factor for hepatocytes:

 Conditioned medium of Swiss 3T3 cells vigorously promoted the growth of hepatocytes. A small protein, pleiotrophin, was isolated from the medium and revealed as a potent mitogen for hepatocytes.

Hair papilla cell specific genes:

 The serial cultivation of hair papilla cells retaining hair-inductibilities was accomplished by culturing them with a conditioned medium of keratinocytes. Using these cells, two papilla-specific and six papilla-preferential gene were isolated.

Artificial skin secreting proinsulin proteins:

 Proinsulin genes were introduced into skin fibroblasts with which artificial skin equivalents were constructed. Diabetic nude mice were implanted with the skin equivalents secreting proinsulin, which resulted in a decrease of their blood-sugar levels and an increase in their body weight.

Proteome databases:

  Total proteins from several different tissues, such as liver cells, fibroblasts, or hair papilla cells, were separated by two-dimensional electrophoresis. Isolated protein spots were analyzed with amino acid sequencing and mass spectrometry. These data were collected in proteome databases, which were very useful for comparing complex protein expression patters between different samples.

graph1

·Regeneration and Metamorphosis Newts regenerate their limbs when damaged (left). Anuran tadpoles transform into frogs (right). These are representatives of the reconstitution of the animal body shape.

graph2

·Cells and ECMs Morphology and function of cells are regulated by information given by ECMs (collagens, fibronectin, proteoglycans, etc.).

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