Publications by authors named "Toshitaka Fujisawa"

The last common ancestor of Bilateria and Cnidaria is considered to develop a nervous system over 500 million years ago. Despite the long course of evolution, many of the neuron-related genes, which are active in Bilateria, are also found in the cnidarian Hydra. Thus, Hydra is a good model to study the putative primitive nervous system in the last common ancestor that had the great potential to evolve to a more advanced one.

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Animal evolution is closely linked to the emergence of the nervous system. At present it is unknown how the basic mechanisms of neural induction and formation of central nervous systems evolved. We addressed this question in Nematostella vectensis, a member of cnidarians, the ancient sister group of bilaterians.

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Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone.

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Oocyte maturation and subsequent spawning in hydrozoan jellyfish are generally triggered by light-dark cycles. To examine if the initiation of the maturation process after light stimulus is mediated by neurotransmitters, neuropeptides isolated originally from Hydra magnipapillata were applied to sexually mature female medusae of the hydrozoan jellyfish Cytaeis uchidae. Among the Hydra neuropeptides tested, Hym-53 (NPYPGLW-NH2 ), as well as a nonphysiological peptide, CGLWamide (CGLW-NH2 ), were most effective in inducing oocyte maturation and spawning.

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Peptides, as signaling molecules, play a number of roles in cell activities. An epitheliopeptide, Hym-301, has been described as a peptide involved in morphogenesis in hydra. However, little is known about the intracellular location of the peptide or its specific functions.

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Peptides play a number of crucial roles as signaling molecules in metazoans. In order to elaborate a more complete picture of the roles played by peptides in a single organism, we launched the "Hydra Peptide Project". For this project, we used Hydra magnipapillata, a species belonging to Cnidaria, one of the most basal metazoan phyla, and using a peptidomic approach, we systematically identified a number of peptide signaling molecules, their encoding genes and their functions.

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Little is known about how the size of an adult animal is determined and regulated. To investigate this issue in hydra, we altered the body size by surgically removing a part of the body column and/or by axial grafting, and examined changes of column length with time. When the body column was shortened it elongated and resumed the original length within 24-48 h.

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Among 8000-9000 species of Cnidaria, only several dozens of species of Hydrozoa have been found in the fresh water. Hydra is such a fresh water polyp and has been used as a good material for research in developmental biology, regeneration and pattern formation. Although the genus Hydra has only a few ten species, its distribution is cosmopolitan.

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The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration.

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Little is known about peptides that control developmental processes such as cell differentiation and pattern formation in metazoans. The cnidarian Hydra is one of the most basal metazoans and is a key model system for studying the peptides involved in these processes. We developed a novel peptidomic approach to the isolation and identification of functional signalling peptides from Hydra (the Hydra peptide project).

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It has been convincingly shown that peptides play important roles in the regulation and maintenance of a variety of tissues and organs in living animals. However, little is known concerning the potential role of peptides as signaling molecules in developmental processes. In Hydra, there is circumstantial evidence that small diffusible molecules act as morphogens in the regulation of patterning processes.

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Cnidarians are widely regarded as one of the first organisms in animal evolution possessing a nervous system. Conventional histological and electrophysiological studies have revealed a considerable degree of complexity of the cnidarian nervous system. Thanks to expressed sequence tags and genome projects and the availability of functional assay systems in cnidarians, this simple nervous system is now genetically accessible and becomes particularly valuable for understanding the origin and evolution of the genetic control mechanisms underlying its development.

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From an evolutionary point of view, Hydra has one of the most primitive nervous systems among metazoans. Two different groups of peptides that affect neuron differentiation were identified in a systematic screening of peptide signaling molecules in Hydra. Within the first group of peptides, a neuropeptide, Hym-355, was previously shown to positively regulate neuron differentiation.

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A systematic screening of peptide signaling molecules (<5000 da) in Hydra magnipapillata (the Hydra Peptide Project) was launched in 1993 and at least the first phase of the project ended in 2007. From the project a number of interesting suggestions and results have been obtained. First, a simple metazoan-like Hydra appears to contain a few hundred peptide signaling molecules: half of them neuropeptides and the rest epitheliopeptides that are produced by epithelial cells.

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In the course of systematic identification of peptide signaling molecules combined with the expressed sequence tag database from Hydra, we have identified a novel neuropeptide family that consists of two members with FRamide at the C-terminus; FRamide-1 (IPTGTLIFRamide) and FRamide-2 (APGSLLFRamide). The precursor sequence deduced from cDNA contained a single copy each of FRamide-1 and FRamide-2 precursor sequences. Expression analysis by whole-mount in situ hybridization showed that the gene was expressed in a subpopulation of neurons that were distributed throughout the body from tentacles to basal disk.

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Cell lineages of cnidarians including Hydra represent the fundamental cell types of metazoans and provides us a unique opportunity to study the evolutionary diversification of cell type in the animal kingdom. Hydra contains epithelial cells as well as a multipotent interstitial cell (I-cell) that gives rise to nematocytes, nerve cells, gland cells, and germ-line cells. We used cDNA microarrays to identify cell type-specific genes by comparing gene expression in normal Hydra with animals lacking the I-cell lineage, so-called epithelial Hydra.

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The digestive tract of Bilateria is a tube with a mouth at one end and an anus at the other end. Radiata, that include the phylum Cnidaria, have a blind-sac form of digestive tract with only one opening. It has therefore been commonly believed that the evolution of the body plan from Radiata to Bilateria included the change of the digestive tract from a blind sac to a tube.

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The hydrozoan is the simplest organism whose movements are governed by the neuromuscular system, and its de novo morphogenesis can be easily induced by the removal of body parts. These features make the hydrozoan an excellent model for studying the regeneration of tissues in vivo, especially in the nervous system. Although glycosaminoglycans (GAGs) and proteoglycans (PGs) have been implicated in the signaling functions of various growth factors and play critical roles in the development of the central nervous system, the isolation and characterization of GAGs from hydrozoans have never been reported.

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Aging occurs in most multicellular animals, yet some primitive animals do not show any sign of aging. This raises the following question: How have metazoans acquired the trait of aging in the course of evolution? Comparative studies of various species have provided a clue to this question by showing that sexually reproducing organisms predominantly undergo aging. The evolutionary theory "pleiotropy" also postulates aging as a price for facilitating the reproduction in the early life stage of an organism.

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Hym-301 is a peptide that was discovered as part of a project aimed at isolating novel peptides from hydra. We have isolated and characterized the gene Hym-301, which encodes this peptide. In an adult, the gene is expressed in the ectoderm of the tentacle zone and hypostome, but not in the tentacles.

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Cell-cell interactions and cell rearrangements play important roles during development. Aggregates of Hydra cells reorganize into the two epithelial layers and subsequently form a normal animal. Examination of the formation of the two layers under various situations, indicates that the motility of endodermal epithelial cells, but not the differential adhesive forces of the two types of epithelial cells, plays the critical role in setting up the two epithelial layers.

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