Menu

Close

millepattes micropeptides are an ancient developmental switch required for embryonic patterning

Suparna Ray, Miriam I Rosenberg, Hélène Chanut-Delalande, Amelie Decaras, Barbara Schwertner, William Toubiana, Tzach Auman, Irene Schnellhammer, Matthias Teuscher, Abderrahman Khila, Martin Klingler, François Payre

Preprint posted on September 03, 2018 https://www.biorxiv.org/content/early/2018/09/03/376111

Atavism in action: an evo-devo study in insects reveals a conserved segmentation role for a post-translational regulatory module.

Selected by Erik Clark

Context

Micropeptides (very short proteins) play important roles in development, but have received relatively little attention thus far. One well-characterised exception is the set of peptides encoded by the insect-specific millepattes (mlpt) gene [a.k.a. tarsalless (tal) or polished rice (pri) in Drosophila]. Mlpt peptides recruit a ubiquitin ligase, Ubr3, to a transcription factor called Shavenbaby (Svb) [a.k.a. Ovo], targeting its N-terminal repression domain for cleavage by the proteasome. This post-translational modification turns Svb into an activator, changing its regulation of downstream genes.

Mlpt, Svb, and Ubr3 therefore form a functional module, because production of the activator form of Svb depends on coincident expression of all three components. Accordingly, perturbing any of the three components leads to similar sets of phenotypes – for example, pri, svb, and ubr3 mutants all cause a loss of denticles in the Drosophila larval cuticle.

Interestingly, the mlpt locus was first identified through a dramatic segmentation phenotype in the beetle Tribolium, but no comparable segmentation function has been found for tal/pri or svb in Drosophila. In Tribolium, Mlpt seems to be involved in the switch from thoracic to abdominal segmentation, as RNAi against mlpt results in truncated embryos with extra pairs of legs (“mille-pattes” means “centipede” in French!) Now, this preprint explores the conservation of this segmentation role across insects.

Key findings

Ray, Rosenberg and colleagues analysed the function of mlpt, svb, and ubr3 in a number of non-drosophilid model insects – namely Tribolium, the true bugs Gerris and Oncopeltus, and the parasitoid wasp Nasonia – using CRISPR and RNAi. In each case they found that all three genes were implicated in segmentation, epidermal patterning, and proximo-distal patterning of the legs, indicating that the Mlpt/Svb/Ubr3 module is conserved across hundreds of millions of years of evolution, and plays a similar set of developmental roles in diverse insects.

They also analysed the expression of the three genes by in situ hybridisation. ubr3 is ubiquitously expressed in embryos, but mlpt and svb exhibit dynamic and largely complementary expression patterns, presumably restricting the Svb activator form to the few tissues and stages where mlpt and svb domains overlap. Significantly, the timing and location of the segmentation-related expression domains seemed to correlate with the onset of sequential segment addition in each species (rather than with a given axial position), suggesting that the Mlpt/Svb/Ubr3 module might be involved in triggering a developmental switch between simultaneous and sequential modes of segment patterning.

RNAi knockdown demonstrates that the segmentation and leg patterning roles of mlpt, svb, and ubr3 are conserved in the hemipteran bugs Gerris and Oncopeltus. Reproduced from Figure 3 of Ray et al. 2018 under a CC-BY 4.0 international license.

But how to explain the lack of a segmentation phenotype in Drosophila? Although mlpt [tal/pri] has a stripy expression pattern in the Drosophila blastoderm, suggestive of a link to segmentation, maternal svb expression fades early in embryogenesis, meaning that Mlpt and Svb activity does not normally overlap. However, the authors found that misexpression of Svb during segmentation stages resulted in a disruption to segment patterning, indicating that although the Drosophila Mlpt/Svb/Ubr3 module no longer plays an active role in segmentation, it retains an ancestral potential to regulate segmentation genes.

Significance

The findings in this study are an important reminder that in many respects the Drosophila embryo is a poor model for insect segmentation. Genes like mlpt and svb have lost their segmentation roles in Drosophila, although they seem to be intact in most other insects. In addition, the clear importance of post-translational regulatory processes in these other insects contrasts with the mainly transcriptional level of regulation characterised for Drosophila segmentation.

However, it’s important to note that it’s still not at all clear what the Mlpt/Svb/Ubr3 module actually does to regulate segmentation! Based on their current observations, the preprint authors raise the intriguing hypothesis of the Mlpt/Svb/Ubr3 module being a developmental switch between simultaneous and sequential segmentation modes, which will make for a fascinating follow-up project. Ironically, an obvious place to start the investigation will be with the Drosophila blastoderm; identifying direct targets of the Mlpt/Svb/Ubr3 module by determining which segmentation genes are the first to be misregulated in the presence of ectopic Svb.

Related Research

Zanet J, Benrabah E, Li T, Pélissier-Monier A, Chanut-Delalande H, Ronsin B, Bellen HJ, Payre F, Plaza S. (2015) Pri sORF peptides induce selective proteasome-mediated protein processing. Science 349(6254):1356-1358

Savard J, Marques-Souza H, Aranda M, Tautz D. (2006). A segmentation gene in Tribolium produces a polycistronic mRNA that codes for multiple conserved peptides. Cell 126(3): 559-569

Rosenberg MI, Brent AE, Payre F, and Desplan C. (2014). Dual mode of embryonic development is highlighted by expression and function of Nasonia pair-rule genes. eLife 3:e01440.

Tags: drosophila, micropeptides, nasonia, oncopeltus, segmentation, shaven-baby, smorfs, tribolium

Posted on: 12th September 2018 , updated on: 13th September 2018

Read preprint (No Ratings Yet)




  • Have your say

    Your email address will not be published. Required fields are marked *

    This site uses Akismet to reduce spam. Learn how your comment data is processed.

    Sign up to customise the site to your preferences and to receive alerts

    Register here

    Also in the developmental biology category:

    Functional characterization of Arabidopsis ARGONAUTE 3 in reproductive tissue

    Pauline E Jullien, Stefan Grob, Antonin Marchais, et al.



    Selected by Chandra Shekhar Misra

    Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

    Mark E. Lush, Daniel C. Diaz, Nina Koenecke, et al.

    AND

    Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

    Eric D Thomas, David Raible



    Selected by Rudra Nayan Das

    1

    Force inference predicts local and tissue-scale stress patterns in epithelia

    Weiyuan Kong, Olivier Loison, Pruthvi Chavadimane Shivakumar, et al.



    Selected by Sundar Naganathan

    Embryo geometry drives formation of robust signaling gradients through receptor localization

    Zhechun Zhang, Steven Zwick, Ethan Loew, et al.



    Selected by Diana Pinheiro

    Unlimited genetic switches for cell-type specific manipulation

    Jorge Garcia-Marques, Ching-Po Yang, Isabel Espinosa-Medina, et al.



    Selected by Rafael Almeida

    1

    Applications, Promises, and Pitfalls of Deep Learning for Fluorescence Image Reconstruction

    Chinmay Belthangady , Loic A. Royer



    Selected by Romain F. Laine

    Maintenance of spatial gene expression by Polycomb-mediated repression after formation of a vertebrate body plan

    Julien Rougot, Naomi D Chrispijn, Marco Aben, et al.



    Selected by Yen-Chung Chen

    1

    The coordination of terminal differentiation and cell cycle exit is mediated through the regulation of chromatin accessibility

    Yiqin Ma, Daniel J McKay, Laura Buttitta



    Selected by Gabriel Aughey

    1

    Embryo geometry drives formation of robust signaling gradients through receptor localization

    Zhechun Zhang, Steven Zwick, Ethan Loew, et al.



    Selected by Paul Gerald L. Sanchez and Stefano Vianello

    Symmetry breaking in the embryonic skin triggers a directional and sequential front of competence during plumage patterning

    Richard Bailleul, Carole Desmarquet-Trin Dinh, Magdalena Hidalgo, et al.



    Selected by Alexa Sadier

    A SOSEKI-based coordinate system interprets global polarity cues in Arabidopsis

    Saiko Yoshida, Alja van der Schuren, Maritza van Dop, et al.



    Selected by Martin Balcerowicz

    1

    Suppressor of Fused controls perinatal expansion and quiescence of future dentate adult neural stem cells

    Hirofumi Noguchi, Jesse Garcia Castillo, Kinichi Nakashima, et al.



    Selected by Ekaterina Dvorianinova

    The embryonic transcriptome of Arabidopsis thaliana

    Falko Hofmann, Michael A Schon, Michael D Nodine



    Selected by Chandra Shekhar Misra

    1

    The cell wall regulates dynamics and size of plasma-membrane nanodomains in Arabidopsis.

    Joseph Franics McKenna, Daniel Rolfe, Stephen E D Webb, et al.



    Selected by Marc Somssich

    Psychiatric risk gene NT5C2 regulates protein translation in human neural progenitor cells

    Rodrigo R.R. Duarte, Nathaniel D. Bachtel, Marie-Caroline Cotel, et al.



    Selected by Joanna Cross

    A Scube2-Shh feedback loop links morphogen release to morphogen signaling to enable scale invariant patterning of the ventral neural tube

    Zach Collins, Kana Ishimatsu, Tony Tsai, et al.



    Selected by Teresa Rayon

    1

    Also in the evolutionary biology category:

    Symmetry breaking in the embryonic skin triggers a directional and sequential front of competence during plumage patterning

    Richard Bailleul, Carole Desmarquet-Trin Dinh, Magdalena Hidalgo, et al.



    Selected by Alexa Sadier

    Bridging the divide: bacteria synthesizing archaeal membrane lipids

    Laura Villanueva, F. A. Bastiaan von Meijenfeldt, Alexander B. Westbye, et al.

    AND

    Extensive transfer of membrane lipid biosynthetic genes between Archaea and Bacteria

    Gareth A. Coleman, Richard D. Pancost, Tom A. Williams



    Selected by Gautam Dey

    1

    PUMILIO hyperactivity drives premature aging of Norad-deficient mice

    Florian Kopp, Mehmet Yalvac, Beibei Chen, et al.



    Selected by Carmen Adriaens

    Eukaryotic acquisition of a bacterial operon

    Jacek Kominek, Drew T. Doering, Dana A. Opulente, et al.



    Selected by Lauren Neves

    millepattes micropeptides are an ancient developmental switch required for embryonic patterning

    Suparna Ray, Miriam I Rosenberg, Hélène Chanut-Delalande, et al.



    Selected by Erik Clark

    Conserved phosphorylation hotspots in eukaryotic protein domain families

    Marta J Strumillo, Michaela Oplova, Cristina Vieitez, et al.



    Selected by Gautam Dey

    Peculiar features of the plastids of the colourless alga Euglena longa and photosynthetic euglenophytes unveiled by transcriptome analyses

    Kristina Zahonova, Zoltan Fussy, Erik Bircak, et al.



    Selected by Ellis O'Neill

    1

    The Ly6/uPAR protein Bouncer is necessary and sufficient for species-specific fertilization

    Sarah Herberg, Krista R Gert, Alexander Schleiffer, et al.



    Selected by James Gagnon

    Timed collinear activation of Hox genes during gastrulation controls the avian forelimb position

    Chloe Moreau, Paolo Caldarelli, Didier Rocancourt, et al.



    Selected by Wouter Masselink

    The genomic basis of colour pattern polymorphism in the harlequin ladybird

    Mathieu Gautier, Junichi Yamaguchi, Julien Foucaud, et al.



    Selected by Fillip Port

    Altering the temporal regulation of one transcription factor drives sensory trade-offs

    Ariane Ramaekers, Simon Weinberger, Annelies Claeys, et al.



    Selected by Mariana R.P. Alves

    A robust method for transfection in choanoflagellates illuminates their cell biology and the ancestry of animal septins

    David Booth, Heather Middleton, Nicole King



    Selected by Maya Emmons-Bell

    A SoxB gene acts as an anterior gap gene and regulates posterior segment addition in the spider Parasteatoda tepidariorum

    Christian L. B. Paese, Anna Schoenauer, Daniel J. Leite, et al.



    Selected by Erik Clark

    1

    Germ layer specific regulation of cell polarity and adhesion gives insight into the evolution of mesoderm.

    Miguel Salinas-Saavedra, Amber Q. Rock, Mark Q. Martindale



    Selected by ClaireS & SophieM

    1

    Wnt/β-catenin regulates an ancient signaling network during zebrafish scale development

    Andrew J Aman, Alexis N Fulbright, David M Parichy



    Selected by Andreas van Impel

    Bacteriophage cooperation suppresses CRISPR-Cas3 and Cas9 immunity

    Adair L Borges, Jenny Y Zhang, MaryClare Rollins, et al.

    AND

    Anti-CRISPR phages cooperate to overcome CRISPR-Cas immunity

    Mariann Landsberger, Sylvain Gandon, Sean Meaden, et al.



    Selected by Fillip Port

    Also in the genetics category:

    MRE11-RAD50-NBS1 activates Fanconi Anemia R-loop suppression at transcription-replication conflicts

    Emily Yun-Chia Chang, James P Wells, Shu-Huei Tsai, et al.



    Selected by Katie Weiner

    1

    Super-resolution Molecular Map of Basal Foot Reveals Novel Cilium in Airway Multiciliated Cells

    Quynh Nguyen, Zhen Liu, Rashmi Nanjundappa, et al.



    Selected by Robert Mahen

    Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

    Mark E. Lush, Daniel C. Diaz, Nina Koenecke, et al.

    AND

    Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

    Eric D Thomas, David Raible



    Selected by Rudra Nayan Das

    1

    The coordination of terminal differentiation and cell cycle exit is mediated through the regulation of chromatin accessibility

    Yiqin Ma, Daniel J McKay, Laura Buttitta



    Selected by Gabriel Aughey

    1

    Ribosomal DNA and the rDNA-binding protein Indra mediate non-random sister chromatid segregation in Drosophila male germline stem cells

    George Watase, Yukiko Yamashita



    Selected by Maiko Kitaoka

    A non-canonical arm of UPRER mediates longevity through ER remodeling and lipophagy.

    Joseph R Daniele, Ryo Higuchi-Sanabria, Vidhya Ramachandran, et al.



    Selected by Sandra Malmgren Hill

    Psychiatric risk gene NT5C2 regulates protein translation in human neural progenitor cells

    Rodrigo R.R. Duarte, Nathaniel D. Bachtel, Marie-Caroline Cotel, et al.



    Selected by Joanna Cross

    The Toll pathway inhibits tissue growth and regulates cell fitness in an infection-dependent manner

    Federico Germani, Daniel Hain, Denise Sternlicht, et al.



    Selected by Rohan Khadilkar

    Rapid embryonic cell cycles defer the establishment of heterochromatin by Eggless/SetDB1 in Drosophila

    Charles A Seller, Chun-Yi Cho, Patrick H O'Farrell



    Selected by Gabriel Aughey

    Evidence for an Integrated Gene Repression Mechanism based on mRNA Isoform Toggling in Human Cells

    Ina Hollerer, Juliet C Barker, Victoria Jorgensen, et al.



    Selected by Clarice Hong

    Signaling dynamics control cell fate in the early Drosophila embryo

    Heath E Johnson, Stanislav Y Shvartsman, Jared E Toettcher



    Selected by Yara E. Sánchez Corrales

    1

    PUMILIO hyperactivity drives premature aging of Norad-deficient mice

    Florian Kopp, Mehmet Yalvac, Beibei Chen, et al.



    Selected by Carmen Adriaens

    Arterio-Venous Remodeling in the Zebrafish Trunk Is Controlled by Genetic Programming and Flow-Mediated Fine-Tuning

    Ilse Geudens, Baptiste Coxam, Silvanus Alt, et al.



    Selected by Andreas van Impel

    CRISPR/Cas9-mediated gene deletion of the ompA gene in an Enterobacter gut symbiont impairs biofilm formation and reduces gut colonization of Aedes aegypti mosquitoes

    Shivanand Hegde, Pornjarim Nilyanimit, Elena Kozlova, et al.



    Selected by Snehal Kadam

    millepattes micropeptides are an ancient developmental switch required for embryonic patterning

    Suparna Ray, Miriam I Rosenberg, Hélène Chanut-Delalande, et al.



    Selected by Erik Clark

    Neural crest cells regulate optic cup morphogenesis by promoting extracellular matrix assembly

    Chase Dallas Bryan, Rebecca Lynne Pfeiffer, Bryan William Jones, et al.



    Selected by Ashrifia Adomako-Ankomah

    1

    Close