Monitoring neural progenitor fate through multiple rounds of division in an intact vertebrate brain

The behaviour of neural progenitors in the intact vertebrate brain and spinal cord is poorly understood, chiefly because of the inaccessibility and poor optical qualities inherent in many model systems. To overcome these problems we have studied the optically superior brain of the zebrafish embryo and have monitored the in vivo behaviour of fluorescently labelled neural progenitors and their daughter cells throughout a substantial period of hindbrain development. We find the majority (84%) of hindbrain neurons are born from progenitor divisions that generate two neurons and 68% of reconstructed lineage trees contained no asymmetric stem cell-like divisions. No progenitors divided in the manner expected of a classic stem cell; i.e. one that repeatedly self-renews and generates a differentiated cell type by asymmetric division. We also analysed the orientation of progenitor divisions relative to the plane of the ventricular zone (VZ) and find that this does not correlate with the fate of the daughter cells. Our results suggest that in this vertebrate system the molecular determinants that control whether a cell will become a neuron are usually not linked to a mechanism that generates asymmetric divisions.