Distinct regulation of atonal in a visual organ of Drosophila : Organ-specific enhancer and lack of autoregulation in the larval eye

Abstract

Drosophila has three types of visual organs, the larval eyes or Bolwig’s organs (BO), the ocelli (OC) and the compound eyes (CE). In all, the bHLH protein Atonal (Ato) functions as the proneural factor for photoreceptors and effects the transition from progenitor cells to differentiating neurons. In this work, we investigate the regulation of ato expression in the BO primordium (BOP). Surprisingly, we find that ato transcription in the BOP is entirely independent of the shared regulatory DNA for the developing CE and OC. The core enhancer for BOP expression, atoBO, lies ~6 kb upstream of the ato gene, in contrast to the downstream location of CE and OC regulatory elements. Moreover, maintenance of ato expression in the neuronal precursors through autoregulation-a common and ancient feature of ato expression that is well-documented in eyes, ocelli and chordotonal organs-does not occur in the BO. We also show that the atoBO enhancer contains two binding sites for the transcription factor Sine oculis (So), a core component of the progenitor specification network in all three visual organs. These binding sites function in vivo and are specifically bound by So in vitro. Taken together, our findings reveal that the control of ato transcription in the evolutionarily derived BO has diverged considerably from ato regulation in the more ancestral compound eyes and ocelli, to the extent of acquiring what appears to be a distinct and evolutionarily novel cis-regulatory module.

All in the family: proneural bHLH genes and neuronal diversity

“…Could other mechanisms thus be used to replace autoregulation to maintain stable neural fate? Positive autoregulation has not been found in studies of some Drosophila neurons, indicating that although the segregation of initiation and autoregulation provides an important conceptual insight into mechanisms of fate specification, similar outcomes might also be achieved by other regulatory mechanisms (Holohan et al, 2006;Zhou et al, 2017). It is possible that transcription factors further downstream are responsible.…”

Serial electron microscopic reconstruction of the drosophila larval eye: Photoreceptors with a rudimentary rhabdomere of microvillar-like processes

“…By contrast, BO PRCs, once segregated from the surface, turn down the expression of the apical/subapical protein complexes Crb and Arm/β-catenin. One might speculate that the disappearance of these proteins is controlled at the transcriptional level, by the emergence of larval-specific cis-regulatory elements, as shown recently shown for the proneural gene atonal (Zhou et al, 2017). In the absence of apical markers, like Crb, PLP or Asl, the polarity of BO PRCs is difficult to follow; using the fact that PRC axons mark the basal pole, and interpreting the opposite side of the cell as the apical pole, one can infer that cells rotate, so that the apical pole faces anteriorly during stage 14/15, and comes to point laterally (i.e., 180 deg rotated from the original orientation) by stage 16 (see Fig.…”

“…Drosophila larval vision, mediated by the BO, has been the focus of several recent functional studies, including (Essen et al, 2011;Humberg et al, 2018;Humberg and Sprecher, 2017;Justice et al, 2012;Kane et al, 2013;Keene et al, 2011). The BO, due to its simplicity in terms of cell types and rapid development during the embryonic period, has also a rich source for developmental genetic analysis (Sprecher et al, 2007;Sprecher and Desplan, 2008;Vasiliauskas et al, 2011;Mishra et al, 2013Mishra et al, , 2016Zhou et al, 2017). To further aid in these studies a more detailed understanding of the ultrastructural details of the BO photoreceptor membrane specializations is required.…”

Patterning mechanisms diversify neuroepithelial domains in the Drosophila optic placode

“…The ventroposterior domain gives rise to the primordium of the larval eye and consists of two photoreceptor (PR) precursor types (primary and secondary precursors), whereas the dorsal domain harbors neuroepithelial precursors that generate the optic lobe of the adult visual system [ 4 – 6 ]. The basic helix-loop-helix transcription factor Atonal (Ato) promotes PR precursor cell fate in the larval eye primordium [ 4 , 7 ]. The orphan nuclear receptor Tailless (Tll) is confined to the optic lobe primordium and maintains non-PR cell fate [ 4 ].…”

“…Notch delimits the number of PR precursors and maintains a pool of non-PR precursors [ 10 ]. Ato is initially expressed in all PR precursors in the placode and its expression gets progressively restricted to primary precursors [ 7 , 11 ]. In a second step, primary precursors recruit secondary precursors via EGFR signaling: primary precursors express the EGFR ligand Spitz, which is required in secondary precursors to promote their survival.…”