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Control of neuronal morphogenesis by homeoproteins: consequences for the making of neuronal networks. Export

Perspectives in Developmental Neurobiology, Vol. 1 (1993), pp. 133-138.

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article c38d46 caenorhabditis_elegans caenorhabditis_elegans_embryology caenorhabditis_elegans_genetics celegans c_elegans cell_nucleus_metabolism dna_binding_proteins_genetics dna_binding_proteins_physiology drosophila_melanogaster_embryology drosophila_melanogaster_genetics elegans f01d46 genes_homeo_box lin-11 mec-3 mice_embryology mice_genetics models_biological morphogenesis_genetics motor_neurons_cytology nematode nerve_net_embryology neurites_ultrastructure neurons_cytology pal-1 transcription_factors_genetics transcription_factors_physiology transfection wormbase zc2473

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To test whether homeoproteins can act as genetic regulators in the processes of neurite growth, branching, guidance, and connectivity, the 60 amino acid homeodomain of Antennapedia was introduced in embryonic neurons in primary culture. It was hoped that this homeopeptide would bind to specific promoters and thus behave as a competitive inhibitor of endogenous homeoproteins. The introduction of the homeodomain in the nerve cells was made easy by its unexpected capability to translocate through the membranes and to accumulate within the nuclei. The presence of the homeodomain within the cells correlated with an increase in neurite growth and branching. The absence of activity of mutant peptides, still internalized but unable to bind with high affinity to homeoprotein cognate binding sites, strongly suggested that endogenous homeoproteins modulate neurite outgrowth and branching. Moreover, the efficient internalization of the homeobox peptide by live cells in culture raises the possibility that, in addition to their well-established role as cell-autonomous transcription factors, some homeoproteins may also exert paracrine functions. We examine how these hypotheses could modify our current views on the establishment and plasticity of neuronal networks.


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