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

doi: https://doi.org/10.1242/prelights.4728

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

preLists in the developmental biology category:

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020

 



List by Jesus Victorino

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.

 



List by Alex Eve

Society for Developmental Biology 79th Annual Meeting

Preprints at SDB 2020

 



List by Irepan Salvador-Martinez, Martin Estermann

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka, Madhuja Samaddar, Miguel V. Almeida, Sejal Davla, Jennifer Ann Black, Gautam Dey

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Preprint missing? Don't hesitate to let us know.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar, Ramona Jühlen, Amanda Haage, Laura McCormick, Maiko Kitaoka

EDBC Alicante 2019

Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.

 



List by Sergio Menchero, Jesus Victorino, Teresa Rayon, Irepan Salvador-Martinez

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Gautam Dey

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.

 



List by Alex Eve

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London

 



List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.

 



List by Alexa Sadier

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Gautam Dey

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.

 



List by Shikha Nayar
Close