Regulatory logic driving stable levels of defective proventriculus expression during terminal photoreceptor specification in flies

Abstract

How differential levels of gene expression are controlled in postmitotic neurons is poorly understood. In the Drosophila retina, expression of the transcription factor Defective Proventriculus (Dve) at distinct cell type-specific levels is required for terminal differentiation of color-and motion-detecting photoreceptors. Here, we find that the activities of two cis-regulatory enhancers are coordinated to drive dve expression in the fly eye. Three transcription factors act on these enhancers to determine cell-type specificity. Negative autoregulation by Dve maintains expression from each enhancer at distinct homeostatic levels. One enhancer acts as an inducible backup ('dark' shadow enhancer) that is normally repressed but becomes active in the absence of the other enhancer. Thus, two enhancers integrate combinatorial transcription factor input, feedback and redundancy to generate cell type-specific levels of dve expression and stable photoreceptor fate. This regulatory logic may represent a general paradigm for how precise levels of gene expression are established and maintained in post-mitotic neurons.

Natural variation in stochastic photoreceptor specification and color preference in Drosophila

“…p R7s lacking Ss signal to p R8s to activate expression of blue-detecting Rhodopsin5 (Rh5). y R7s expressing Ss do not send this signal, resulting in expression of green-detecting Rhodopsin6 (Rh6) in y R8s ( Figure 1A ) ( Franceschini et al, 1981 ; Montell et al, 1987 ; Zuker et al, 1987 ; Chou et al, 1996 ; Huber et al, 1997 ; Chou et al, 1999a ; Mikeladze-Dvali et al, 2005 ; Mazzoni et al, 2008 ; Vasiliauskas et al, 2009 ; Jukam and Desplan, 2011 ; Hsiao et al, 2013 ; Johnston, 2013 ; Jukam et al, 2013 ; Jukam et al, 2016 ; Yan et al, 2017 ).…”

Buffering and Amplifying Transcriptional Noise During Cell Fate Specification

“…Indeed, a weak shadow enhancer can act additively with its primary enhancer to control transcriptional bursting and reduce expression noise ( Bothma et al, 2015 ). Other forms of shadow enhancers, such as “dark” shadow enhancers promote robust expression patterns through the combinatorial use of enhancers and negative feedback ( Yan et al, 2017 ).…”

Interactions with presynaptic photoreceptors mediated by the Dpr11 and DIP-γ cell surface proteins control selection and survival of Drosophila amacrine neurons

“…To assess Dm8 subtypes in the reverse situation where there are only pR7 in the eye, we ectopically expressed the Defective proventriculus (Dve) transcription factor, a repressor downstream of ss, in all PRs (Johnston et al, 2011;Nakagawa et al, 2011;Yan et al, 2017).…”