transcription, migration, heart, head muscles, actin dynamics, vesicle trafficking, cell polarity, cell-cell communication, asymmetric cell divisions

Lionel Christiaen
Professor of Biology
Education
- 2004 Ph.D. (Molecular & Cellular Developmental Biology), Universite Paris XI (Orsay)
- 1997 B.S., Ecole Normale Superieure/Universite Paris VI
Transcriptional control of collective cell migration in the cardio-pharyngeal mesoderm of ascidian embryos
Our long-term research goal is to understand how tissue-specific gene regulatory networks control and coordinate the basic processes underlying cell behavior during morphogenesis. We study the migrating cells of the cardiogenic mesoderm in embryos of the ascidian Ciona intestinalis as a model system to investigate this problem.
Ascidians are Tunicates, the closest living relatives to vertebrates and they display a simplified but typical chordate body plan during embryonic and larval stages. Ascidian embryos offer several advantages for experimental studies of developmental gene activities and cell behavior. First, they develop with a reduced number of cells with invariant lineages that have been determined up to the pre-gastrula 110 cell stage. This allows one to visualize developmental events with a sub-cellular resolution using live microscopy. Second, extensive genomic and expression resources are readily available through user-friendly web interfaces. This facilitates functional studies utilizing microinjection of antisense morpholino oligonucleotides and an experimental tool unique to ascidians among metazoans: the simultaneous electroporation of hundreds of fertilized eggs with synthetic plasmid DNA constructs, which permits cis-regulatory analyses using reporter genes and targeted expression of recombinant and/or fluorescent proteins using tissue-specific enhancers for functional studies and fluorescent microscopy.
In ascidians, the trunk ventral cells (TVCs) migrate from the anterior part of the tail to the ventral part of the trunk in tailbud embryos and constitute the precardiac mesoderm. They originate from a single pair of blastomeres in the early embryo, called B7.5 cells. The B7.5 blastomeres give birth to the TVCs and their sister cells, the anterior tail muscles (ATMs), which differentiate into skeletal muscle and do not migrate. Previous studies showed that TVC-specific gene expression and migration require transcriptional inputs from the bHLH transcription factor Mesp, the FGF signaling pathway and the forkhead transcription factor FoxF. Because of these functional evidences, TVC migration constitutes a suitable model system to investigate the relationship between transcription regulation and directed cell migration. To this aim, we use a method combining fluorescence activated cell sorting (FACS) and microarray analysis to obtain TVC-specific whole genome transcription profiles. These data indicated that the gene regulatory network impinges on most cellular processes underlying cell migration (e.g. actin dynamics, cell-matrix adhesion, polarity and vesicle trafficking) through transcriptional regulation of subsets of the effector genes (Christiaen et al., 2008).
After this first migration, bilateral pairs of TVCs merge at the midline and divide asymmetrically along the medio-lateral axis to give birth to the (median) heart and (lateral) atrial siphon muscle (ASM) precursors. Strikingly, the four ASM precursors on each side of the heart primordium undergo a second collective migration towards the dorso-lateral atrial siphon placode in the ectoderm. We found that this second migration is regulated by an ASM-specific transcription factor, the Collier/Olf1/Ebf ortholog COE (Stolfi et al., 2010).
Our current research focuses on:
- The cellular and molecular mechanisms that establish and maintain collective cell polarization during TVC migration. We study the gene regulatory network downstream of FoxF, the regulated effector genes, the polarized cellular processes and the extrinsic signals influencing TVC polarity.
- The cellular and molecular mechanisms controlling heart vs. ASM fate specification and ASM collective migration. We study the regulation of COE in the TVC lineage. We obtained whole-genome transcription profiles for heart and ASM precursors. We use these data to compare TVC and ASM migrations and identify migration-specific effector genes and regulatory network modules.
Date of these PubMed search results: March 24 2020
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- Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices.
Elife (2019 Nov 20) PMC6952182 free full-text archive
Racioppi C, Wiechecki KA, Christiaen L - A conserved regulatory program initiates lateral plate mesoderm emergence across chordates.
Nat Commun (2019 Aug 26) PMC6710290 free full-text archive
Prummel KD, Hess C, Nieuwenhuize S, Parker HJ, Rogers KW, Kozmikova I, Racioppi C, Brombacher EC, Czarkwiani A, Knapp D, Burger S, Chiavacci E, Shah G, Burger A, Huisken J, Yun MH, Christiaen L, Kozmik Z, Muller P, Bronner M, Krumlauf R, Mosimann C - A single-cell transcriptional roadmap for cardiopharyngeal fate diversification.
Nat Cell Biol (2019 Jun) PMID: 31160712
Wang W, Niu X, Stuart T, Jullian E, Mauck WM 3rd, Kelly RG, Satija R, Christiaen L - A complete statistical model for calibration of RNA-seq counts using external spike-ins and maximum likelihood theory.
PLoS Comput Biol (2019 Mar) PMC6428340 free full-text archive
Athanasiadou R, Neymotin B, Brandt N, Wang W, Christiaen L, Gresham D, Tranchina D - Initial characterization of Wnt-Tcf functions during Ciona heart development.
Dev Biol (2019 Apr 15) PMC6487219 free full-text archive
Kaplan NA, Wang W, Christiaen L - Discoidin-domain receptor coordinates cell-matrix adhesion and collective polarity in migratory cardiopharyngeal progenitors.
Nat Commun (2019 Jan 4) PMC6320373 free full-text archive
Bernadskaya YY, Brahmbhatt S, Gline SE, Wang W, Christiaen L - Transcriptional regulation of Rab32/38, a specific marker of pigment cell formation in Ciona robusta.
Dev Biol (2019 Apr 15) PMID: 30471267
Racioppi C, Coppola U, Christiaen L, Ristoratore F - CRISPR Knockouts in Ciona Embryos.
Adv Exp Med Biol (2018) PMC6061950 free full-text archive
Gandhi S, Razy‑Krajka F, Christiaen L, Stolfi A - Purification of Fluorescent Labeled Cells from Dissociated Ciona Embryos.
Adv Exp Med Biol (2018) PMC6020031 free full-text archive
Wang W, Racioppi C, Gravez B, Christiaen L - An FGF-driven feed-forward circuit patterns the cardiopharyngeal mesoderm in space and time.
Elife (2018 Feb 6) PMC5809146 free full-text archive
Razy‑Krajka F, Gravez B, Kaplan N, Racioppi C, Wang W, Christiaen L - Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes.
Nat Commun (2017 Nov 27) PMC5703972 free full-text archive
Burguera D, Marquez Y, Racioppi C, Permanyer J, Torres‑Mendez A, Esposito R, Albuixech‑Crespo B, Fanlo L, D'Agostino Y, Gohr A, Navas‑Perez E, Riesgo A, Cuomo C, Benvenuto G, Christiaen LA, Marti E, D'Aniello S, Spagnuolo A, Ristoratore F, Arnone MI, Garcia‑Fernandez J, Irimia M - ANISEED 2017: extending the integrated ascidian database to the exploration and evolutionary comparison of genome-scale datasets.
Nucleic Acids Res (2018 Jan 4) PMC5753386 free full-text archive
Brozovic M, Dantec C, Dardaillon J, Dauga D, Faure E, Gineste M, Louis A, Naville M, Nitta KR, Piette J, Reeves W, Scornavacca C, Simion P, Vincentelli R, Bellec M, Aicha SB, Fagotto M, Gueroult‑Bellone M, Haeussler M, Jacox E, Lowe EK, Mendez M, Roberge A, Stolfi A, Yokomori R, Brown CT, Cambillau C, Christiaen L, Delsuc F, Douzery E, Dumollard R, Kusakabe T, Nakai K, Nishida H, Satou Y, Swalla B, Veeman M, Volff JN, Lemaire P - Evolutionary loss of melanogenesis in the tunicate Molgula occulta.
Evodevo (2017) PMC5516394 free full-text archive
Racioppi C, Valoroso MC, Coppola U, Lowe EK, Brown CT, Swalla BJ, Christiaen L, Stolfi A, Ristoratore F - Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona.
Dev Biol (2017 May 1) PMC5502750 free full-text archive
Gandhi S, Haeussler M, Razy‑Krajka F, Christiaen L, Stolfi A - Fused Regression for Multi-source Gene Regulatory Network Inference.
PLoS Comput Biol (2016 Dec) PMC5140053 free full-text archive
Lam KY, Westrick ZM, Muller CL, Christiaen L, Bonneau R - Rewiring of an ancestral Tbx1/10-Ebf-Mrf network for pharyngeal muscle specification in distinct embryonic lineages.
Development (2016 Oct 15) PMC5087645 free full-text archive
Tolkin T, Christiaen L - Ciona as a Simple Chordate Model for Heart Development and Regeneration.
J Cardiovasc Dev Dis (2016 Sep) PMC5023151 free full-text archive
Anderson HE, Christiaen L - Transcriptional Control of Developmental Cell Behaviors.
Annu Rev Cell Dev Biol (2016 Oct 6) PMID: 27501446
Bernadskaya Y, Christiaen L - Migratory neuronal progenitors arise from the neural plate borders in tunicates.
Nature (2015 Nov 19) PMC4654654 free full-text archive
Stolfi A, Ryan K, Meinertzhagen IA, Christiaen L - A new heart for a new head in vertebrate cardiopharyngeal evolution.
Nature (2015 Apr 23) PMC4851342 free full-text archive
Diogo R, Kelly RG, Christiaen L, Levine M, Ziermann JM, Molnar JL, Noden DM, Tzahor E - Regulation and evolution of cardiopharyngeal cell identity and behavior: insights from simple chordates.
Curr Opin Genet Dev (2015 Jun) PMC4470797 free full-text archive
Kaplan N, Razy‑Krajka F, Christiaen L - Surrounding tissues canalize motile cardiopharyngeal progenitors towards collective polarity and directed migration.
Development (2015 Feb 1) PMC4303000 free full-text archive
Gline S, Kaplan N, Bernadskaya Y, Abdu Y, Christiaen L - Tissue-specific genome editing in Ciona embryos by CRISPR/Cas9.
Development (2014 Nov) PMC4302896 free full-text archive
Stolfi A, Gandhi S, Salek F, Christiaen L - Guidelines for the nomenclature of genetic elements in tunicate genomes.
Genesis (2015 Jan) PMC4308547 free full-text archive
Stolfi A, Sasakura Y, Chalopin D, Satou Y, Christiaen L, Dantec C, Endo T, Naville M, Nishida H, Swalla BJ, Volff JN, Voskoboynik A, Dauga D, Lemaire P - Divergent mechanisms regulate conserved cardiopharyngeal development and gene expression in distantly related ascidians.
Elife (2014 Sep 10) PMC4356046 free full-text archive
Stolfi A, Lowe EK, Racioppi C, Ristoratore F, Brown CT, Swalla BJ, Christiaen L - Fibroblast growth factor signalling controls nervous system patterning and pigment cell formation in Ciona intestinalis.
Nat Commun (2014 Sep 5) PMC4164782 free full-text archive
Racioppi C, Kamal AK, Razy‑Krajka F, Gambardella G, Zanetti L, di Bernardo D, Sanges R, Christiaen LA, Ristoratore F - Collier/OLF/EBF-dependent transcriptional dynamics control pharyngeal muscle specification from primed cardiopharyngeal progenitors.
Dev Cell (2014 May 12) PMC4045103 free full-text archive
Razy‑Krajka F, Lam K, Wang W, Stolfi A, Joly M, Bonneau R, Christiaen L - NK4 antagonizes Tbx1/10 to promote cardiac versus pharyngeal muscle fate in the ascidian second heart field.
PLoS Biol (2013 Dec) PMC3849182 free full-text archive
Wang W, Razy‑Krajka F, Siu E, Ketcham A, Christiaen L - Cis-regulatory timers for developmental gene expression.
PLoS Biol (2013 Oct) PMC3812112 free full-text archive
Christiaen L - p120RasGAP mediates ephrin/Eph-dependent attenuation of FGF/ERK signals during cell fate specification in ascidian embryos.
Development (2013 Nov) PMC4007711 free full-text archive
Haupaix N, Stolfi A, Sirour C, Picco V, Levine M, Christiaen L, Yasuo H - Genetic and genomic toolbox of the chordate Ciona intestinalis.
Genetics (2012 Sep) PMC3430545 free full-text archive
Stolfi A, Christiaen L - Development and evolution of the ascidian cardiogenic mesoderm.
Curr Top Dev Biol (2012) PMID: 22449842
Tolkin T, Christiaen L - Developmental cell behavior.
Semin Cell Dev Biol (2012 May) PMID: 22445735
Christiaen L - Transcriptional enhancers in ascidian development.
Curr Top Dev Biol (2012) PMID: 22305162
Wang W, Christiaen L - Early chordate origins of the vertebrate second heart field.
Science (2010 Jul 30) PMC4970750 free full-text archive
Stolfi A, Gainous TB, Young JJ, Mori A, Levine M, Christiaen L - The ANISEED database: digital representation, formalization, and elucidation of a chordate developmental program.
Genome Res (2010 Oct) PMC2945195 free full-text archive
Tassy O, Dauga D, Daian F, Sobral D, Robin F, Khoueiry P, Salgado D, Fox V, Caillol D, Schiappa R, Laporte B, Rios A, Luxardi G, Kusakabe T, Joly JS, Darras S, Christiaen L, Contensin M, Auger H, Lamy C, Hudson C, Rothbacher U, Gilchrist MJ, Makabe KW, Hotta K, Fujiwara S, Satoh N, Satou Y, Lemaire P - A cis-regulatory signature for chordate anterior neuroectodermal genes.
PLoS Genet (2010 Apr 15) PMC2855326 free full-text archive
Haeussler M, Jaszczyszyn Y, Christiaen L, Joly JS - Isolation of individual cells and tissues from electroporated sea squirt (Ciona) embryos by fluorescence-activated cell sorting (FACS).
Cold Spring Harb Protoc (2009 Dec) PMID: 20150096
Christiaen L, Wagner E, Shi W, Levine M - Whole-mount in situ hybridization on sea squirt (Ciona intestinalis) embryos.
Cold Spring Harb Protoc (2009 Dec) PMID: 20150095
Christiaen L, Wagner E, Shi W, Levine M - Microinjection of morpholino oligos and RNAs in sea squirt (Ciona) embryos.
Cold Spring Harb Protoc (2009 Dec) PMID: 20150094
Christiaen L, Wagner E, Shi W, Levine M - X-gal staining of electroporated sea squirt (Ciona) embryos.
Cold Spring Harb Protoc (2009 Dec) PMID: 20150093
Christiaen L, Wagner E, Shi W, Levine M - Electroporation of transgenic DNAs in the sea squirt Ciona.
Cold Spring Harb Protoc (2009 Dec) PMID: 20150092
Christiaen L, Wagner E, Shi W, Levine M - Isolation of sea squirt (Ciona) gametes, fertilization, dechorionation, and development.
Cold Spring Harb Protoc (2009 Dec) PMID: 20150091
Christiaen L, Wagner E, Shi W, Levine M - The sea squirt Ciona intestinalis.
Cold Spring Harb Protoc (2009 Dec) PMID: 20150076
Christiaen L, Wagner E, Shi W, Levine M - BMP signaling coordinates gene expression and cell migration during precardiac mesoderm development.
Dev Biol (2010 Apr 15) PMID: 19913008
Christiaen L, Stolfi A, Levine M - Spatio-temporal intersection of Lhx3 and Tbx6 defines the cardiac field through synergistic activation of Mesp.
Dev Biol (2009 Apr 15) PMID: 19389354
Christiaen L, Stolfi A, Davidson B, Levine M - The transcription/migration interface in heart precursors of Ciona intestinalis.
Science (2008 Jun 6) PMID: 18535245
Christiaen L, Davidson B, Kawashima T, Powell W, Nolla H, Vranizan K, Levine M - FoxF is essential for FGF-induced migration of heart progenitor cells in the ascidian Ciona intestinalis.
Development (2007 Sep) PMID: 17720694
Beh J, Shi W, Levine M, Davidson B, Christiaen L - Evolutionary modification of mouth position in deuterostomes.
Semin Cell Dev Biol (2007 Aug) PMID: 17656139
Christiaen L, Jaszczyszyn Y, Kerfant M, Kano S, Thermes V, Joly JS - FGF signaling delineates the cardiac progenitor field in the simple chordate, Ciona intestinalis.
Genes Dev (2006 Oct 1) PMC1578698 free full-text archive
Davidson B, Shi W, Beh J, Christiaen L, Levine M - Linking chordate gene networks to cellular behavior in ascidians.
Cell (2006 Jan 27) PMID: 16439196
Davidson B, Christiaen L - The dopamine-synthesizing cells in the swimming larva of the tunicate Ciona intestinalis are located only in the hypothalamus-related domain of the sensory vesicle.
Eur J Neurosci (2005 Jun) PMID: 15978015
Moret F, Christiaen L, Deyts C, Blin M, Joly JS, Vernier P - Regulatory gene expressions in the ascidian ventral sensory vesicle: evolutionary relationships with the vertebrate hypothalamus.
Dev Biol (2005 Jan 15) PMID: 15617694
Moret F, Christiaen L, Deyts C, Blin M, Vernier P, Joly JS - A modular cis-regulatory system controls isoform-specific pitx expression in ascidian stomodaeum.
Dev Biol (2005 Jan 15) PMID: 15617693
Christiaen L, Bourrat F, Joly JS - Embryonic versus blastogenetic development in the compound ascidian Botryllus schlosseri: insights from Pitx expression patterns.
Dev Dyn (2005 Feb) PMID: 15614778
Tiozzo S, Christiaen L, Deyts C, Manni L, Joly JS, Burighel P - Culture of adult ascidians and ascidian genetics.
Methods Cell Biol (2004) PMID: 15575606
Hendrickson C, Christiaen L, Deschet K, Jiang D, Joly JS, Legendre L, Nakatani Y, Tresser J, Smith WC - Pitx genes in Tunicates provide new molecular insight into the evolutionary origin of pituitary.
Gene (2002 Apr 3) PMID: 11992728
Christiaen L, Burighel P, Smith WC, Vernier P, Bourrat F, Joly JS
Contact Information
Lionel Christiaen
Professor of Biology lc121@nyu.edu Brown Building31 Washington Place
Room 951B
New York, NY 10003
Phone: (212) 998-8490