Mitotic sympathetic neuroblasts initiate axonal pathfinding in vivo

Neuronal precursor proliferation and axodendritic outgrowth have been tradi tionally regarded as discrete and sequential developmental stages, However, we recently found that sympathetic neuroblasts in vitro often elaborate lo ng neuritic processes before dividing. Furthermore, these "paramitotic" neu rites were maintained during cell division and neuritic morphology was cons istently preserved by daughter cells after mitosis, This inheritance of neu ritic morphology in vitro raised the possibility that proliferating neurobl asts engage in axodendritic outgrowth, To determine whether mitotic superio r cervical ganglion (SCG) neuroblasts are engaged in pathfinding in vivo, w e have combined retrograde axonal tracing of efferent nerve trunks with bro modeoxyuridine (BrdU) labeling of cells in S-pha je. In fact, about 13% of BrdU(+) cells were retrogradely labeled, indicating that mitotic neuroblast s often have extraganglionic axonal projections. Moreover, the presence of axons during S-phase was observed at two developmental ages (E15.5 and E16. 5), implicating an ongoing function of paramitotic axone during neuronal on togeny, Using a calculation to account for experimental limitations,,ve est imate that virtually all mitotic SCG neuroblasts have direct access to extr aganglionic signals during development, We conclude that mitotic neuronal p recursors in vice engage in pathfinding, raising the possibility that inter action of proliferating populations with distant signals actively coordinat es cell division and neural connectivity. (C) 1999 John Wiley & Sons, Inc. J Neurobiol 40: 366-374, 1999.