Parallel gene expression orders during segmentation (top) and neurogenesis (bottom) determine cell fate.


Click! Even as a snapshot records a moment in time, so too do the progeny of neuronal stem cells record and remember the transcriptional regulatory factors present at the time of their birth. For it is these factors that determine the cells' fate—their temporal identity and spatial destiny.

In the fly, the genes hunchback (hb), pdm1/pdm2 (pdm), and castor (cas) are expressed at different times in the embryonic central nervous system and have been suggested to specify temporal identity of neuroblast daughter cells. Now, Chris Doe and colleagues (University of Oregon, Eugene, OR) propose that sequential expression of these factors defines identity in neuroblast lineages.

Doe and colleagues first add the gene krüppel (Kr) to the proposed temporal cassette, and find that individual lineages sequentially make Hb, then Kr, then Pdm, and finally Cas. Hb and Kr are necessary and sufficient to specify the fate of first- and second-born progeny, respectively.

Birth order, not cell type, correlates with the layered expression of these gene. Thus, the same sequence of gene expression is followed regardless of whether the original progeny cell is a motorneuron, interneuron, or glial cell. First-born progeny express Hb and occupy the deepest cortical layers, whereas second-born progeny express Kr and reside in the next deepest layer.

A cell-cycle dependent clock, rather than a global timing mechanism, appears to regulate the sequential expression of these genes. If the cell cycle is stopped, the sequence of changes in gene expression also stops. ▪


Isshiki, T., et al.