Figure 1. Temporal patterning of Drosophila neuroblasts.

(A) Temporal patterning in embryonic and larval stage VNC and central brain type I neuroblasts. The embryonic VNC NBs sequentially express Hb, Kr, Pdm, Cas and Grh, which control the birth-order dependent progeny fate specification. Usually the two daughters of a GMC adopt different fates due to Notch dependent binary fate choices. This is a simplified and generalized model, and there are slight variations of temporal patterning in different NB linages (Doe, 2017). In certain NB lineages, there is another stage in which Cas and Grh are co-expressed. At the embryo to larva transition, some NBs exit the cell cycle, while others enter quiescence and become re-activated at the larval stage. Early larval TTFs Cas and Svp are required for the transition between RNA-binding proteins Imp and Syncrip that form opposing gradients. In at least some NBs, the transition is regulated by Ecdysone or Activin signaling. Late larval TTFs in the Syncrip window include Br and E93 is some NB lineages. (B) Temporal patterning in type II neuroblast lineages. In addition to the NB temporal axis, there is a second INP temporal axis. INPs sequentially express D, Grh, Hbn, Ey and Scro as they undergo self-renewing asymmetric divisions to generate GMCs which divide to produce neurons. Combinatorial temporal patterning greatly expands neural diversity. (C) Temporal patterning in medulla neuroblasts. Medulla neuroblasts sequentially express TTFs that control the sequential generation of different cell fates through regulating the expression of neuronal transcription factors. Hth, SoxN and Dmrt99B start their expression in the neuroepithelium, and each of them is required for the expression of Bsh in neurons. Opa is expressed in two waves in NBs and possibly serve as TTF for two different temporal stages. Opa is required for the generation of neurons expressing Run, TfAP-2, or Dac + Dfr (also known as Vvl). Erm and Ey are required for the generation of neurons expressing Kn, or Ap+Dfr. Hbn is required for the generation of neurons expressing Oc and Tj. Scro and Slp are required for the expression of Sox102F; D is required for the expression of Ets65A; and finally Gcm is required for the switch to gliogenesis and cell cycle exit. (D)(E)(F) Cross-regulatory interactions in Drosophila TTF cascades. Green pointed arrows indicate activation, and red flat-headed arrows indicate repression. Arrows with dashed lines indicate that a certain cross-regulation is sufficient but not required for the transition. (D) Cross-regulatory interactions in the embryonic VNC TTF cascade. (E) Regulation of temporal progression in the INP TTF cascade of type II NB lineages. Epigenetic regulators Osa, Ham and a transcription factor Opa are required to regulate the temporal progression in addition to cross-regulations between TTFs. (F) Cross-regulatory interactions in the medulla TTF cascade. Dashed rectangles around Scro and Slp indicates that Ey is required for the activation of both Slp and Scro; while both Slp and Scro are required to repress Ey.