DE-NOVO ACQUISITION OF NEURONAL POLARITY IN RETINOIC ACID-INDUCED EMBRYONAL CARCINOMA-CELLS

The mouse embryonal carcinoma cell line PCC7-Mz1 represents an advanta geous model to study acquisition of polarity by neurons, During the fi rst two days after differentiation is induced by the addition of retin oic acid, the neuronal derivatives develop extensions which for at lea st four more days do not differ from each other in growth characterist ics, morphology, and marker expression, Beginning around differentiati on day 6 and following the relocation of the nucleus from a central to a polar position in the cell soma, the morphology and marker expressi on changes dramatically: expression of MAP2 diminishes and eventually disappears in the thinner neurite (future axon), which originates at t he nucleated pole, but remains strong in the branched, broad based neu rite(s), The opposite changes in expression are observed for synaptoph ysin, together with a clustering of the vesicle protein in varicosity- like areas, Complete segregation of expression of the two markers is a chieved around day 12, shortly followed by dendrite-specific location of MAP2 mRNA and the ability to generate and conduct action potentials , Our studies add several aspects to the process of neuronal polarity acquisition, as it was previously studied in primary cultures of embry onic neurons: (i) we monitored neuronal differentiation from the birth of neurons, rather than from later and less defined maturation stages , (iii cell nucleus relocation may be associated with the induction of neuronal polarity, and (iii) functional competence of neurons is clos ely associated with previous acquisition of polarity, Acquisition of p olarity by PCC7-Mz1 neuronal derivatives probably refers to de novo ac quisition rather than to reestablishment of polarity.