Interdependent regulation of stereotyped and stochastic photoreceptor fates in the fly eye

Abstract

Diversification of neuronal subtypes often requires stochastic gene regulatory mechanisms. How stochastically expressed transcription factors interact with other regulators in gene networks to specify cell fates is poorly understood. The random mosaic of color-detecting R7 photoreceptor subtypes in Drosophila is controlled by the stochastic on/off expression of the transcription factor Spineless (Ss). In Ss ON R7s, Ss induces expression of Rhodopsin 4 (Rh4), whereas in Ss OFF R7s, the absence of Ss allows expression of Rhodopsin 3 (Rh3). Here, we find that the transcription factor Runt, which is initially expressed in all R7s, is sufficient to promote stochastic Ss expression. Later, as R7s develop, Ss negatively feeds back onto Runt to prevent repression of Rh4 and ensure proper fate specification. Together, stereotyped and stochastic regulatory inputs are integrated into feedforward and feedback mechanisms to control cell fate.

Deep Diversity: Extensive Variation in the Components of Complex Visual Systems across Animals

“…In vertebrates, crx , otx2 , and rax are expressed in all PRCs, but different factors control the opsins expressed in rods (nrl, nr2e3, nr1d1, pias 3, and fiz1) compared with cones (thbr and rxrg for Lws opsin; tbx2 for Sws1) [ 26 ]. In insects, a set of genes ( senseless , prospero , spalt , and spineless ) is used for PRC specification, but variation in gene regulatory networks drive differences across a compound eye and between species [ 27 , 28 , 29 ].…”

Insect opsins and evo-devo: what have we learned in 25 years?

“…In the dorsal third retina, lower Dve expression and Iroquois complex expression activate Rh3 coexpression with Rh4 in dorsal yellow ommatidia [16,37,38]. Recently, another feedback loop was discovered, showing that interaction with stereotyped upstream Runt expression contributes to the stochastic Spineless expression that determines pale or yellow ommatidial types [39] (figure 1c). Feedforward, feedback and bistable loops build redundancy and modularity into this system and have become hallmarks of robust developmental processes in other complex traits.…”

Transcriptional priming and chromatin regulation during stochastic cell fate specification

“…Ss is expressed in yR7s where it promotes Rh4 expression and yR7 fate, while suppressing Rh3 expression and pR7 fate [30] (figure 1a,c). Ss interacts with a network of transcription factors to regulate R7 subtype fate [31][32][33][34][35][36]. As Ss ON/OFF expression defines R7 subtype fate, we will refer to Rh3-expressing pR7s as Ss OFF R7s and Rh4-expressing yR7s as Ss ON R7s (figure 1a).…”

“…Key differences lie in the roles of protein-mediated feedback in the final step of fate stabilization. While stochastic ss gene regulation is independent of protein feedback in the fly, transcription network feedback ensures proper expression of Rh4 in ss -expressing R7s [ 14 , 32 ]. In mice, OR feedback is a vital mechanism for OR fate maintenance and OSN maturation, preventing co-expression or fate switching of multiple ORs [ 55 , 70 , 79 , 80 ].…”