Temporal regulation of neural diversity in Drosophila and vertebrates

Abstract

The generation of neuronal diversity involves temporal patterning mechanisms by which a given progenitor sequentially produces multiple cell types. Several parallels are evident between the brain development programs of Drosophila and vertebrates, such as the successive emergence of specific cell types and the use of combinations of transcription factors to specify cell fates. Furthermore, cell-extrinsic cues such as hormones and signaling pathways have also been shown to be regulatory modules of temporal patterning. Recently, transcriptomic and epigenomic studies using large single-cell sequencing datasets have provided insights into the transcriptional dynamics of neurogenesis in the Drosophila and mammalian central nervous systems. We review these commonalities in the specification of neuronal identity and highlight the conserved or convergent strategies of brain development by discussing temporal patterning mechanisms found in flies and vertebrates.

Keywords: Cell identity; Drosophila; Fate specification; Neuronal diversity; Temporal patterning; Vertebrates.

Figure 1:. Temporal transcription factor cascades

A. Schematic showing the larval Drosophila brain and its different components where major neurogenesis events occur: central brain (CB), optic lobe (OL) and ventral nerve cord (VNC). Circles represent neural progenitor cells or neuroblasts. B. Temporal transcription factor (tTF) cascades found in the mouse retina and across different regions of the fly brain including the ventral nerve cord (VNC), central brain (CB), and the optic lobe (OL) (main outer proliferation center: mOPC; tips of the OPC: tOPC). Several orthologous tTFs exist between the fly VNC and the mouse retina including Hb/Ikzf1, Pdm/Pou2f and Cas/Casz1. Newly identified tTFs in the mouse retina, fly mOPC and the fly CB INPs are shown in gray. C. Different cell types in the murine retina are born in a sequential and time-dependent manner from retinal progenitor cells, and the temporal order of their production from embryonic to postnatal stages is illustrated in the graph below. Abbreviations: RGC - Retinal Ganglion Cell, HC - Horizontal Cell, Cone - Cone Photoreceptor Cell, AC - Amacrine Cell, Rod - Rod Photoreceptor Cell, BC - Bipolar Cell and MG - Müller glia (not pictured here). Adapted with permission from [23].

Figure 2:. Parallel temporal programs direct neuronal diversification in the developing fly and mouse visual system

A. Left panel - Single-cell RNA sequencing of the developing Drosophila optic lobe showing neural progenitors (neuroblasts and GMCs) differentiating along a conserved trajectory from neuroepithelial cells to neurons. Right panel - Highlighted region shows canonical tTFs expressed in optic lobe neuroblasts along an orthogonal axis defining the temporal windows of fate specification. Adapted with permission from [ - Konstantinides et al. 2022]. B. Left panel - A similar temporal patterning mechanism is observed in mouse retinogenesis wherein single-cell ATAC sequencing reveals major trajectories of retinal fate specification. Right panel - Retinal progenitors sequentially differentiate from neuroepithelial cells (RPC S1) through distinct competent cell states (RPC S2 and RPC S3) generating retinal neurons, before terminally dividing into Müller glia. Intrinsic and reciprocal TF-TF cross-regulations drive the temporal GRN progression through distinct RPC states by generating (dashed lines) and maintaining (curved arrows) specific cell fates. Abbreviations: NG - Neurogenic Progenitor, RGC - Retinal Ganglion Cell, AC - Amacrine Cell, HC - Horizontal Cell, BC - Bipolar Cell, MG - Müller Glia. Adapted with permission from [ - Lyu et al. 2021].