181 The development of mult~icellular organisms from a single fertilized oocyte proceeds according to a hierarchic, evolutive plan that determines the identity, as well as the spatial and temporal fate of each constituent cell. The analysis of loss of function and gain of function mutants in insects and vertebrates revealed the decisive role of different morphogenetic regulators, such as homeobox and pair-box con- taining intracellular dete~inants, diffusible po~ypeptide growth hormones and a family of low molecular weight ligands that control gene expression via specific nuclear receptors. Morphogenetic regulators may attract and chaperone several endoganous inductors and they may activate either alone or in synergy with other DNA binding factors specific cohorts of genes involved in cell differentiation.
Transcript
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The development of mult~icellular organisms from a single fertilized oocyte proceeds according to a hierarchic, evolutive plan that determines the identity, as well as the spatial and temporal fate of each constituent cell. The analysis of loss of function and gain of function mutants in insects and vertebrates revealed the decisive role of different morphogenetic regulators, such as homeobox and pair-box con- taining intracellular dete~inants, diffusible po~ypeptide growth hormones and a family of low molecular weight ligands that control gene expression via specific nuclear receptors. Morphogenetic regulators may attract and chaperone several endoganous inductors and they may activate either alone or in synergy with other DNA binding factors specific cohorts of genes involved in cell differentiation.
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In invertt;brate organisms, gross developmental fates may be determined by simple diffusible lig- and(s). In insects, for example, the famesyl derivate, Juvenil Hormone, provides the permissive signal of larval development and it plays the veto role for adult tissue cells inhibiting metamorphosis. Carote- noids only play a chromogenic role in many invertebrates; they are converted enzymatically in well bounded groups of cells resulting in marvelous ectodermal patterns in the adult organism (see the stereom- icroscopy view of a butterfly’s wing, Inachis io L x 500).
In vertebrates, carotenoids undergo a further metabolic switch. Retinol became the key visual pig- ment, while several retinoic acid isomers integrate into the morphogenetic regulatory hierarchy. Recent experimental and clinical data confirm that impairments in the morphogenetic regulatory network may lead to malignant transformation thus provin, n Waddington’s hypothesis published in 1935, that cancer may be a developmental disorder.
Differentiation therapy is a conceptually new approach for cancer management, which stems from epidemiological and random screening studies. Therapeutical trials with retinoids, interferon, steroid hor- mone agonists and antagonics have already shown promising results in some specific cases. The iden- tification of new morphogenetic substances, new regulatory mechanisms and the elaboration of combined therapeutic protocols will hopefully lead to important progress in cancer prevention, diagnostics and therapy.
onsors of t eeting
Amgen, UK Ares-Serono, Italy Bristol-Myers Co, Ltd, Japan Chugai Pharmaceutical Co, Ltd, Japan
Eizai Co, Ltd, Japan
Farmitalia Carlo Erba Co, Ltd, Japan Hoffman-La Roche, USA Ici Pharmaceuticals, UK
Kirin Brewery Co, Ltd. Japan Lilly Industries, Ltd, UK Meiji Pharmaceutical Co, Ltd, Japan The National Institutes of Health, USA
