Temporal Patterning in the Drosophila CNS

A small pool of neural progenitors generates the vast diversity of cell types in the CNS. Spatial patterning specifies progenitor identity, followed by temporal patterning within progenitor lineages to expand neural diversity. Recent work has shown that in Drosophila, all neural progenitors (neuroblasts) sequentially express temporal transcription factors (TTFs) that generate molecular and cellular diversity. Embryonic neuroblasts use a lineage-intrinsic cascade of five TTFs that switch nearly every neuroblast cell division; larval optic lobe neuroblasts also use a rapid cascade of five TTFs, but the factors are completely different. In contrast, larval central brain neuroblasts undergo a major molecular transition midway through larval life, and this transition is regulated by a lineage-extrinsic cue (ecdysone hormone signaling). Overall, every neuroblast lineage uses a TTF cascade to generate diversity, illustrating the widespread importance of temporal patterning.

Do mammalian orthologs of the fly TTFs have similar functions? Recent work has shown that the Hb-related gene Ikaros has a role in specifying early-born neuron identity in the mammalian retina and CNS (Alsio et al. 2013, Elliott et al. 2008) and that the Cas-related gene Casz1 specifies late-born identity in the mammalian retina (Mattar et al. 2015). Grh is related to mammalian CP2 domain proteins Grhl1–3, with this family having a conserved function in epithelial biology rather than in temporal patterning (Boglev et al. 2011, Senga et al. 2012). Less is currently known about the mammalian homologs of Kr, Pdm, or the many larval TTFs. Nevertheless, work in Drosophila shows that the use of TTFs to specify temporal identity is widespread, even though the factors can vary from region to region, and thus TTFs are very likely used to generate neuronal diversity in both flies and mammals.