Neuronal Polarity and Morphogenesis

Abstract For a given neuron, the development of its axonal and dendritic arborizations depends on many external factors, such as matrix molecules, growth factors, depolarization, electric fields, and adhesion molecules. In this paper, we summarize and comment on several protocols that can be used to modulate axonal or dendritic elongation and/or modify the shape of the neurites. A first series of protocols is based on the modulation of neuron-substratum adhesion by the addition of extra cellular matrix molecules. Indeed, axons initiate and elongate under low adhesion conditions, whereas dendrites grow only on highly adhesive substrata. A second series of protocols involves the use of drugs affecting the organization of the cytoskeleton. They suggest that the different behaviors of the axonal and dendritic compartments, in particular under low adhesion conditions, are due partly to the organization of the microtubule and actin networks. Third, we describe a protocol based on the internalization of Antennapedia homeodomain that translocates through the cell membrane and is conveyed to neuronal nuclei. Using this technique, we demonstrated that homeoproteins are involved in the morphological differentiation of postmitotic neurons and, in the case of the motoneurons, in axonal elongation. Furthermore, fusion polypeptides up to 109 amino acids and encompassing the 60-amino-acid translocating homeodomain are also transported through the membrane, thus offering a way to introduce exogenous biologically active peptides into live neurons.