Projects

In the team we are developing several projects :

Project 1 : Neural induction in amphioxus

Neural induction is the process by which the pluripotent cells of the ectoderm acquire a neural fate. We have shown that this process in amphioxus as in vertebrates involves a particular region of the embryo called the organizer. We were also able to demonstrate that this process is under the control of the Nodal signalling pathway. Our current objective is to understand the events downstream of the Nodal signal that lead an ectodermal cell to become a neuron. To do this, we use different functional techniques to study the "Gene Regulatory Network" induced by the Nodal pathway during neural induction in amphioxus. This project is funded by the Institut Universitaire de France.

Key publication :

Le Petillon Y, Luxardi G, Scerbo P, Cibois M, Leon A, Subirana L, Irimia M, Kodjabachian L, Escriva H*, Bertrand S*. (2017) Nodal/Activin Pathway is a Conserved Neural Induction Signal in Chordates. Nat Ecol Evol. 2017 Aug;1(8):1192-1200. 

*co-corresponding authors

Figure Project 1 : The dorsal lip of a gastrula blastopore after injection of TexasRed was grafted onto an ectodermic explant which develops into epidermis when grown alone. The host shows an expression of the neural marker Neurogenin, indicating that the graft (red fluorescent) has induced the acquisition of neural fate in cells that normally enter the epidermal differentiation program. Scale bar : 50µM. Modified from : Le Petillon Y et al., Nodal/Activin Pathway is a Conserved Neural Induction Signal in Chordates. Nat Ecol Evol. 2017 Aug;1(8):1192-1200.

Project 2 : Evolution of the vertebrates’ head and somitogenesis

In vertebrates, the mesoderm of the head is unsegmented compared to that of the trunk, which forms repeated structures called somites. In amphioxus, the entire mesoderm is segmented into somites, and this characteristic is proposed to be ancestral in chordates. This implies that the unsegmented character of the anterior mesoderm of vertebrates would be a specific trait of this lineage. We have shown that when the FGF (Fibroblast Growth Factor) signal is inhibited during amphioxus gastrulation, anterior somites do not form. In attempting to define signals downstream of FGF, we have highlighted the existence of three populations of somites in amphioxus whose formation depends on different transcription factors, including Pax3/7 and Six1/2. In vertebrates, somite muscles also form under the control of these factors, while those derived from the mesoderm of the head develop under the control of Tbx1 and Pitx2. This suggests that the mesoderm of the vertebrate head is not directly derived from a paraxial mesoderm that would have lost its segmentation. In an attempt to better understand the evolutionary link between the anterior somites of amphioxus and the mesoderm of the vertebrate head, we analyze more precisely the events downstream of the FGF signal that controls the formation of anterior somites in amphioxus. This project was funded by ANR EVOLONGATION.

Key publications :

Aldea D, Subirana L, Keime C, Meister L, Maeso I, Marcellini S, Gomez-karmeta JL, Bertrand S*, Escriva H*. Genetic regulation of amphioxus somitogenesis informsthe evolution of the vertebrate head mesoderm. Nat Ecol Evol. 2019 Jul1.

 *co-corresponding authors

Bertrand S, Aldea D, Oulion S, Subirana L, de Lera AR, Somorjai I, Escriva H. Evolution of the Role of RA and FGF Signals in the Control of Somitogenesis in Chordates. PLoS One. 2015 Sep 15;10(9):e0136587.

Bertrand S, Camasses A, Somorjai I, Belgacem MR, Chabrol O, Escande ML, Pontarotti P, Escriva H. Amphioxus FGF signaling predicts the acquisition of vertebrate morphological traits. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9160-5.

Figure Projet 2 : In situ hybridizations for MLC (Myosin Light Chain) and MRF1 (Myogenic Regulatory Factor 1) on control embryos and embryos treated with SU5402 during gastrulation. The arrows indicate the anterior limit of expression. This shows that the anterior somites were lost after treatment. Scale bar: 50µm. DV= dorsal view. LV : side view. Modified from: Bertrand S et al., Amphioxus FGF signaling predicts the acquisition of vertebrate morphological traits. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9160-5.

Project 3 : Evolution of developmental regulation in chordates at the genome level

Embryonic development involves communication between cells that use different signals. These signaling pathways control several aspects of cellular activity, including the expression of developmental genes. These signals are present in all animals, but the actors of these pathways and the genes they control are different, resulting in different developmental processes and morphological traits. Our objective is to compare at the genome level the transcriptional regulations controlled by the best characterized signaling pathways in amphioxus and vertebrates using RNA-seq and ATAC-seq approaches. This project is funded by ANR CHORELAND and carried out in collaboration with Jose-Luis Gomez-Skarmeta's team in Seville.

Key publications  :

Bertrand S, Le Petillon Y, Somorjai IML, Escriva H. (2017) Developmental cell-cell communication pathways in the cephalochordate amphioxus: actors and functions. Int J Dev Biol. 2017;61(10-11-12):697-722.

Acemel RD, Tena JJ, Irastorza-Azcarate I, Marlétaz F, Gómez-Marín C, de la Calle-Mustienes E, Bertrand S, Diaz SG, Aldea D, Aury JM, Mangenot S, Holland PW, Devos DP, Maeso I, Escrivá H, Gómez-Skarmeta JL. (2016). A single three-dimensional chromatin compartment in amphioxus indicates a stepwise evolution of vertebrate Hox bimodal regulation. Nat Genet. 2016 Mar;48(3):336-41.

Cross-cutting project: technical development

Our team is a leader in amphioxus developmental studies. In this context, we wish to continue to develop new tools and techniques. We recently obtained the complete genome sequence of the European species Branchiostoma lanceolatum as well as numerous epigenomic data in collaboration with the Genoscope and several international laboratories. This genome and expression data will soon be implemented in the MARIMBA database. Genomic and epigenomic data are available on the AmphiENCODE page and on the UCSC Genome Browser (see the link in the AmphiENCODE page). We have developed in collaboration with several teams the techniques of RNA-seq, ATAC-seq and ChIP-seq and today we are developing mutagenesis through the CRISPR/Cas9 system. These research axes are partly funded by the European projects CORBEL and ASSEMBLEplus.

Key publications :

Escriva H. (2018). My Favorite Animal, Amphioxus: Unparalleled for Studying Early

Vertebrate Evolution. Bioessays. 2018 Dec;40(12):e1800130.

Marlétaz F, Firbas PN, Maeso I, Tena JJ, Bogdanovic O, Perry M, Wyatt CDR, de la Calle-Mustienes E, Bertrand S, Burguera D, Acemel RD, van Heeringen SJ, Naranjo S, Herrera-Ubeda C, Skvortsova K, Jimenez-Gancedo S, Aldea D, Marquez Y, Buono L, Kozmikova I, Permanyer J, Louis A, Albuixech-Crespo B, Le Petillon Y, Leon A, Subirana L, Balwierz PJ, Duckett PE, Farahani E, Aury JM, Mangenot S, Wincker P, Albalat R, Benito-Gutiérrez È, Cañestro C, Castro F, D'Aniello S, Ferrier DEK, Huang S, Laudet V, Marais GAB, Pontarotti P, Schubert M, Seitz H, Somorjai I, Takahashi T, Mirabeau O, Xu A, Yu JK, Carninci P, Martinez-Morales JR, Crollius HR, Kozmik Z, Weirauch MT, Garcia-Fernàndez J, Lister R, Lenhard B,  Holland PWH, Escriva H*, Gómez-Skarmeta JL*, Irimia M*. (2018). Amphioxus functional genomics and the origins of vertebrate gene regulation. Nature. 2018Dec;564(7734):64-70.

*co-corresponding authors

Oulion S, Bertrand S, Belgacem MR, Le Petillon Y, Escriva H. (2012). Sequencing and analysis of the Mediterranean amphioxus (Branchiostoma lanceolatum) transcriptome. PLoS One. 2012;7(5):e36554.

Bertrand S, Escriva H. (2011). Evolutionary crossroads in developmental biology: amphioxus. Development. 2011 Nov;138(22):4819-30. doi: 10.1242/dev.066720. Review.