A neural progenitor mitotic wave is required for asynchronous axon outgrowth and morphology

Abstract

Spatiotemporal mechanisms generating neural diversity are fundamental for understanding neural processes. Here, we investigated how neural diversity arises from neurons coming from identical progenitors. In the dorsal thorax of Drosophila, rows of mechanosensory organs originate from the division of sensory organ progenitor (SOPs). We show that in each row of the notum, an anteromedial located central SOP divides first, then neighbouring SOPs divide, and so on. This centrifugal wave of mitoses depends on cell-cell inhibitory interactions mediated by SOP cytoplasmic protrusions and Scabrous, a secreted protein interacting with the Delta/Notch complex. Furthermore, when this mitotic wave was reduced, axonal growth was more synchronous, axonal terminals had a complex branching pattern and fly behaviour was impaired. We show that the temporal order of progenitor divisions influences the birth order of sensory neurons, axon branching and impact on grooming behaviour. These data support the idea that developmental timing controls axon wiring neural diversity.

Scabrous is distributed via signaling filopodia to modulate Notch response during bristle patterning in Drosophila

“…Scabrous puncta can be observed as far as 2-3 cell diameters away ( 20-30 microns, Figure 1C), although most are localized within 10 microns of the bristle cell nuclei. Together these observations are consistent with previous reports that Scabrous-GFP can localize to the basal signaling filopodia of bristle precursor cells (Lacoste et al, 2022), and that Scabrous acts cell non-autonomously (Renaud and Simpson, 2001). Interestingly, the average length of signaling filopodia extending from the basal surface of bristle precursor cells is 10 µm April 20, 2023 4/13 (Hunter et al, 2019).…”

“…We and others have observed that Scabrous is distributed both apically and basally in the patterning notum. In a previous study, Scabrous was shown to localize along the length of basal signaling filopodia in the patterning notum (Lacoste et al, 2022). It is currently unknown if Scabrous is distributed via these signaling filopodia, or through a diffusion-based process.…”

“…There is evidence that Scabrous is a secreted and diffusible Notch regulator, expressed primarily by Notch-inactive, Delta-expressing bristle precursor cells (Baker et al, 1990;Hu et al, 1995;Lee et al, 1996). Other studies indicate that Scabrous is carried via long, actin-rich signaling filopodia (Chou and Chien, 2002;Lacoste et al, 2022), the activity of which are also implicated in establishing bristle density as discussed above (Cohen et al, 2010;Hunter et al, 2019). Signaling filopodia formation and dynamics are Scabrous independent (Renaud and Simpson, 2001) but both are up-regulated in cells that express high levels of Delta ligand (Buffin and Gho, 2010;de Joussineau et al, 2003).…”

“…The flexibility of cells fates in the tissue helps to ensure a robust sensory organ pattern. Failure to correctly organize the thoracic sensory bristles can lead to changes in fly behavioral responses (Lacoste et al, 2022). Furthermore the spatial distribution of sensory bristles is under selective pressure as Drosophila species exhibit a variety of bristle densities and organizations (Simpson et al, 1999).…”

Segment-specific axon guidance by Wnt/Fz signaling diversifies motor commands inDrosophilalarvae

“…One limitation of this study is that the sample sizes of single-Wave analyses are not high. While clonal analysis has been used to examine fine morphological abnormalities associated with axon guidance defects (Lacoste et al, 2022; Lin et al, 2022; Seroka and Doe, 2019; Xie et al, 2019), these studies were mostly qualitative. This was because the “hit rate” is generally low in this stochastic labelling method.…”