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Our group is interested in understanding how embryonic cells develop into different lineages and go on to form a heart during morphogenesis. Understanding cardiac morphogenesis will allow identifying the mechanisms affected in congenital heart diseases -impacting around 1 live birth in every 100- and inform design principles to program tissue patterns and shape for tissue engineering.
Our heart is composed of four chambers, two ventricles and two atria arranged in parallel and driving blood from the body to the lungs and through the rest of the body. We recently established a fate map demonstrating that each group of cells forming the heart have distinct spatial and temporal origins in the primitive streak (the early embryonic structure that gives rise to mesoderm and endoderm tissues during gastrulation) (PMID: 33999917). The ventricular progenitors are the first to leave the streak, followed by progenitors contributing to the atrium and outflow tract. These observations suggest the cardiac progenitors are prespecified in the primitive streak, prefiguring their allocation to distinct anatomical structures of the heart.
In our latest work, we established new live-imaging methods using light-sheet and multiphoton technologies to enable simultaneous recording of cell migration and intracellular signal transduction pathways during gastrulation in the mouse (see ). The analysis is complemented by single-cell RNA sequencing and bar-coding, allowing us to distinguish differentiation trajectories between wildtype听and mutant progenitors. We are also investigating if, depending on timing and sites of ingression through the primitive streak, cardiac progenitors adopt distinct migratory routes that expose them to signalling at distinct developmental time points, thus influencing their cardiac fate and morphogenesis.
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- Group听Members
Marehiko Kondo
Research Assistant - St Georges University
marehiko.kondo@ucl.ac.ukShayma Abukar听
BHF PhD student
shayma.abukar.22@ucl.ac.uk
UCL Profiles Page:
- Selected Publications
Original Articles:
1.Shayma听Abukar,听Peter听Embacher,听Alessandro听Cicarrelli,听Sunita听Varsani-Brown,听Jamie A听Dean,听James听Briscoe,听Kenzo听Ivanovitch* Live-imaging reveals Coordinated Cell Migration and Cardiac Fate Determination during Mammalian Gastrulation. bioRxiv听2023.12.19.572445;听doi.org/10.1101/2023.12.19.572445
2.听M. Joaquina Del谩s, Christos M Kalaitzis, Tamara Fawzi, Madeleine Demuth, Isabel Zhang, Hannah T Stuart, Elena Costantini, Kenzo Ivanovitch, Elly M Tanaka, James Briscoe. Developmental cell fate choice employs two distinct cis regulatory strategies.听Developmental Cell听2022.06.06.494792;听doi.org/10.1016/j.devcel.2022.11.016听
3.听Ivanovitch K*, Soro-Barrio P, Chakravarty P, Jones RA, Mousavy Gharavy SN, Stamataki D, Delile J, Smith J.C, Briscoe J. Ventricular, atrial and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak.听PLOS Biology听doi.org/10.1371/journal.pbio.3001200 (2021)
4.听Collart C., Ciccarelli A.,听Ivanovitch K.,听Rosewell I., Kumar S., Kelly G., Edwards A., Smith J.C. The migratory pathway of the cells that form the endocardium, dorsal aortae, and head vasculature in the mouse embryo.听BMC Dev Biol听21,听8 (2021)
5.听Metzis V, Steinhauser S, Pakanavicius E, Gouti N, Stamataki D,听Ivanovitch K, Watson T, Rayon T, Neda Mousavy Gharavy S, Robin Lovell-Badge, Nicholas M Luscombe and James Briscoe. Nervous System Regionalization Entails Axial Allocation before Neural Differentiation.听Cell听Oct 2018 Nov 1;175(4):1105-1118.e17.
6.听Ivanovitch K, Temino Valbuena Susana, Torres M. Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis.听eLife听Dec 2017;6:e30668
7.听Le Garrec JF, Dominguez JN, Desgrange A,听Ivanovitch K, Raphael E, Bangham JA, Torres M, Coen E, Mohun TJ and Meilhac SM. A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics听eLife听Nov 2017;6:e28951
8.听Diz-Munoz A, Romanczuk P, Yu W, Bergert M,听Ivanovitch K, Salbreux G, Heisenberg CP, Paluch EK. Steering cell migration by alternating blebs and actin-rich protrusions.听BMC Biol. 2016 Sep 2;14(1):74.
9.听Ivanovitch K, Cavodeassi F, Wilson SW. Precocious acquisition of neuroepithelial character in the eye field underlies the early onset of eye morphogenesis.听Developmental Cell听2013 Nov, (27), 293-305
10.听Cavodeassi F,听Ivanovitch K, Wilson SW. Eph/Ephrin signalling maintains eye field segregation from adjacent neural territories during forebrain morphogenesis.听Development听2013 Oct 140, 4193-4202
11.听Picone R, Ren X,听Ivanovitch K, Clarke JDW, McKendry RA, Baum B. A Polarised Population of Dynamic Microtubules Mediates Homeostatic Length Control in Animal Cells.听PLoS Biol. 2010 Nov 16;8(11)
12.听Tamori Y, Bialucha CU, Tian AG, Kajita M, Huang YC, Norman M, Harrison N, Poulton J,听Ivanovitch K, Disch L, Liu T, Deng WM, Fujita Y. Involvement of Lgl and Mahjong/VprBP in cell competition.听PLoS Biol.听2010 Jul 13;8(7)
13.听Fichelson P, Moch C,听Ivanovitch K, Martin C, Sidor CM, Lepesant JA, Bellaiche Y, Huynh JR. Live imaging of single stem cells within their niche reveals that a U3snoRNP component segregates asymmetrically and is required for self-renewal in Drosophila.听听Nat Cell Biol.听2009 Jun;11(6):678-9
Review Article:
1.听Ivanovitch, K; Esteban, I.; Torres, M. Growth and Morphogenesis during Early Heart Development in Amniotes.听J. Cardiovasc. Dev. Dis.听2017 Nov 22;4(4):20.
