Temporal Patterning in the Drosophila CNS

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Temporal Patterning in the Drosophila CNS

Annual Review of Cell and Developmental Biology

Vol. 33:219-240 (Volume publication date October 2017)
https://doi.org/10.1146/annurev-cellbio-111315-125210

Chris Q. Doe

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Abstract

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.

Keywords

temporal identity, neuroblast, neural stem cell, neural diversity, subtemporal

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  • Figures
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Figure 1  (a) Stage 10 embryo flat mounted and stained for Snail protein to identify brain, thorax, and abdominal neuroblasts (NBs). (b) Third-instar larval brain and thoracic CNS stained for Deadpan to identify the indicated pools of NBs. (c) Three modes of NB cell division. The largest cells are NBs. Abbreviations: GMC, ganglion mother cell; INP, intermediate neural progenitor; n, neurons [all sibling neurons are either NotchON (n*) or NotchOFF (n)].

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Figure Locations

...and optic lobe NBs segregate from the edge of an optic lobe epithelium during larval stages—the only NBs formed postembryonically (Figure 1a,b)....

...All Drosophila NBs undergo molecularly asymmetric cell divisions to generate a series of smaller progeny, using three modes of division (Figure 1c)....

...which undergo a terminal division to make NotchON and NotchOFF sibling neurons; Figure 1c)....

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Figure 2  Temporal patterning in embryonic neuroblasts. The horizontal lines represent gene expression over time (early to late from left to right); the dashed lines represent lower-level expression. The “Cell type” rows indicate the neuron(s) born from each ganglion mother cell (GMC). The “Markers” rows indicate the molecular markers that distinguish neurons within a lineage. Abbreviations: INs, interneurons of unknown identity; PCD, programmed cell death; s, sibling cell of unknown identity. Citations to expression data are given in the text.

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Figure Locations

...temporal patterning has been studied in 8 of the 30 VNC NBs (Figure 2). ...

...NB3-5) (Isshiki et al. 2001, Moris-Sanz et al. 2014, Novotny et al. 2002, Pearson & Doe 2003, Tran & Doe 2008) (Figure 2)....

...Some NB lineages generate two or three GMCs during the Hb expression window (Figure 2), ...

...NB3-1) (Cleary & Doe 2006, Isshiki et al. 2001, Tran & Doe 2008) (Figure 2)....

...and Pdm+ Cut+ RP5 ventral-projecting motor neurons (Tran & Doe 2008) (Figure 2)....

...with Tv2–Tv4 made during the second Cas window (which is Cas+ Grh+) (Figure 2)....

...Thus, ABLK likely forms during the Cas/Grh expression window (Figure 2)....

...and NB5-3 lineages (Gabilondo et al. 2011, Grosskortenhaus et al. 2006, Lai & Doe 2014, Tsuji et al. 2008) (Figure 2)....

...Although many other genes are expressed in neurons of a known birth order (see Figure 2), ...

...an early post-Hb pulse and a later pulse following Tv1 neuron birth (Figure 2)....

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Figure 3  Temporal patterning in larval neuroblasts (NBs). Where known, hours after larval hatching are shown at the top. The lines at the top of each panel represent gene expression over time (early to late from left to right). The identity of each line is color coded with the gene name above [for example, in the mushroom body (MB) NB panel, Imp is shown in dark green, whereas Chinmo is shown in light green]. In the indicated NB population, line gradients reflect approximate expression gradients. Downward arrows indicate that the NB temporal factor is required to specify a particular neuronal identity, lack of an arrow indicates a correlation only between NB factor expression and a specific neuronal identity, a T bar indicates an inhibitory relationship, and curved upward arrows in the anterodorsal (AD) NB panel indicate the cell fate transformations occurring in the absence of Kr or Chinmo. In the AD NB panel, E denotes embryo, and L denotes larva. The “Cell type” row indicates the neuron(s) born during each expression window. The “Markers” row indicates the molecular markers that distinguish neurons within a lineage. The “Progeny” row in the thoracic NB panel indicates temporal expression in NB progeny. Abbreviations: MNs, motor neurons; OPC, outer proliferation center; tOPC, tip OPC.

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Figure Locations

...The AD NB generates 18 different projection neuronal subtypes during its embryonic lineage and an additional 22 neuronal subtypes during its larval lineage (Kao et al. 2012) (Figure 3). Kr mutant clones generated in the AD NB result in a highly specific loss of the eleventh fate—the VA7l neuron—whereas clones generated in the GMC precursor to this neuron show a transformation of the eleventh fate to the twelfth fate (VA7l to VA2) (Kao et al. 2012)....

...Each lab identified candidate TTFs with sequential but overlapping expression in NBs as they age from young to old (Li et al. 2013, Suzuki et al. 2013): Homothorax (Hth) → Klumpfuss (Klu) → Eyeless (Ey) → Sloppy paired 1 and 2 (Slp1 and Slp2) → Dichaete (D) → Tailless (Tll) (Figure 3)....

...using Dll instead of Hth as the first factor and dropping the Tll expression window (Bertet et al. 2014) (Figure 3)....

...subdividing the lineages into early and late components; a few more narrowly expressed factors create diversity within early and late neuronal populations (Figure 3)....

...and old NBs have low Imp and high Syp expression (Liu et al. 2015) (Figure 3)....

...and Abrupt is required to specify α′/β′ neuronal identity (Kucherenko & Shcherbata 2013) (Figure 3)....

...which generates 40 different projection neuron subtypes characterized by their unique innervation of antennal lobe glomeruli (Jefferis et al. 2001, Yu et al. 2010). chinmo mutant clones transform the thirteenth–fifteenth fates to the sixteenth fate (DM3 neuron) and transform the seventeenth–twenty-first fates to the twenty-second fate (D neuron) (Kao et al. 2012) (Figure 3)....

...These motor neurons have a stereotyped birth order between 22 and 66 h after larval hatching (ALH), probably falling into the Chinmo+ neuronal window (Figure 3)....

...and Svp in the early phase and Broad and E93 (Eip93: Flybase) during the late phase (Syed et al. 2017) (Figure 3)....

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