Mitotic neuroblasts determine neuritic patterning of progeny

Neuronal precursor proliferation and axodendritic outgrowth have been regarded as strictly sequential, with process formation presumably beginning after mitotic activity ceases. We now report that sympathetic precursors in vitro often elaborate long neurites before dividing. Of 437 neuroblasts observed in 48 time-lapse recordings, 42 neuroblasts divided. Thirty (71%) of these mitotic neuroblasts had neurites prior to cytokinesis. "Paramitotic" neurites were found to contain microtubules (MTs), indicating that precursors elaborate neuritic cytoskeleton during proliferation. Remarkably, the precise neuritic pattern exhibited by parental neuroblasts was consistently reproduced by daughter cell pairs. Preservation of neuritic morphology occurred through asymmetric division, with individual neurites allocated to specific daughter cells. Paramitotic neurites either remained intact throughout mitosis (12 of 65), or "retracted" into the soma during prophase and then "regrew" within minutes after cytokinesis (53 of 65). "Retraction" and "regrowth" involved resorption of cytoplasm into the soma, then refilling of residual cell membrane, resulting in recapitulation of the parental neurite pattern. Paramitotic neuritogenesis appears to be intrinsically driven, but is responsive to environmental signals. The culture substrate influenced neurite length, but not the response of paramitotic neurites during mitosis or the preservation of neuritic morphology. However, the incidence of neurite-bearing neuroblasts increased from 38 +/- 1.3% to 94 +/- 1.1% with growth factor treatment. The surprisingly high incidence of paramitotic neurites and the fidelity with which patterning was conserved across cell generations raise the possibility that mitotic precursors engage in pathfinding. Our studies suggest a novel link between neurogenesis and cytoarchitectonic patterning.