The mlpt/Ubr3/Svb module comprises an ancient developmental switch for embryonic patterning

Abstract

Small open reading frames (smORFs) encoding ‘micropeptides’ exhibit remarkable evolutionary complexity. Conserved peptides encoded by mille-pattes (mlpt)/polished rice (pri)/tarsal less (tal) are essential for embryo segmentation in Tribolium but, in Drosophila, function in terminal epidermal differentiation and patterning of adult legs. Here, we show that a molecular complex identified in Drosophila epidermal differentiation, comprising Mlpt peptides, ubiquitin-ligase Ubr3 and transcription factor Shavenbaby (Svb), represents an ancient developmental module required for early insect embryo patterning. We find that loss of segmentation function for this module in flies evolved concomitantly with restriction of Svb expression in early Drosophila embryos. Consistent with this observation, artificially restoring early Svb expression in flies causes segmentation defects that depend on mlpt function, demonstrating enduring potency of an ancestral developmental switch despite evolving embryonic patterning modes. These results highlight the evolutionary plasticity of conserved molecular complexes under the constraints of essential genetic networks.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

Multiple roles of the polycistronic genetarsaless/mille-pattes/polished-riceduring embryogenesis of the kissing bugRhodnius prolixus

“…melanogaster, the expression occurs in seven blastodermal stripes, a pair-rule pattern, while in most other insect species, including the basally branching Diptera midge Clogmia albipunctata, the expression appears as a gap domain [13]. Thus, as observed for T. castaneum [6] and more recently in the hemiptera Oncopeltus fasciatus [33], Rpmlpt is first expressed in an anterior domain overlapping with the head and shortly after also in a posterior domain overlapping with the prospective thoracic segments (Figure 4).…”

“…Recent data suggest that an ancient regulatory system involving an Mlpt/Ubr3/Svb module operates in several insect species and overlapping expression domains of mlpt and svb have been reported [33]. Finally, Rp-Notch expression is downregulated upon Rpmlpt RNAi ( Figure 5).…”

Shavenbaby protein isoforms orchestrate the self-renewalversusdifferentiation ofDrosophilaintestinal stem cells

“…Ubr3 then induces the processing of Svb via limited proteasome degradation of its N-terminal repression domain (see Figure 2C). Originally described in epidermal derivatives (Chanut-Delalande et al, 2014;Kondo et al, 2010), a growing body of evidence suggests that Pri-dependent processing underlies Svb function in somatic tissues (Pueyo and Couso, 2011;Ray et al, 2019), including adult stem cells (Bohere et al, 2018).…”

“…A main aspect of Svb regulation relies on post-translational control of its transcriptional activity (Bohere et al, 2018;Chanut-Delalande et al, 2014;Kondo et al, 2010;Menoret et al, 2013;Ray et al, 2019;Zanet et al, 2015). Svb processing into an activator is indispensable for the maintenance of stem cells, which otherwise undergo apoptosis.…”

“…The switch between Svb REP and Svb ACT is triggered by Pri small peptides throughout the fly life-cycle (Bohere et al, 2018;Chanut-Delalande et al, 2014;Kondo et al, 2010;Zanet et al, 2015) and across arthropods (Ray et al, 2019;Savard et al, 2006). pri expression is manifest in progenitors but absent from differentiated enterocytes, and Pri peptides are required, together with their target Ubr3 ubiquitin ligase, for stem cell maintenance.…”