Our research is focused on the crosstalk between cell and tissue-scale mechanics and biochemical signaling to regulate developmental programs and cellular mechanisms in the embryo, including cell/tissue morphogenesis and polarization, cell-cell adhesion, cell migration, cell fate specification and tissue patterning events. To answer these questions, we are using quantitative live cell imaging, biophysical force measurements, biochemical and genetic tools, genomics/transcriptomics and mathematical modeling from subcellular, to tissue level. We are utilizing the zebrafish embryo as a vertebrate model system to study these questions due to transparency and rapid development ex utero, facilitating in vivo live cell imaging, chemical and mechanical perturbations and cell/tissue isolation for in vitro assays.
The current research focus is on two main events during zebrafish gastrulation: the first process comprises the early development of the prospective anterior neural plate (ANP), where neural precursor cells (neurectoderm) become positioned and specified along the embryonic axes into specific domains to contribute to the formation of the central nervous system (CNS). We are interested in unraveling the role of mechanical forces in neurectoderm cell/tissue morphogenesis, movement and cell specification/tissue patterning to develop a functional CNS. The second event involves the coordinated movements of internalized mesendoderm (prechordal plate) cells, which migrate as a cell collective towards the animal pole of the embryo and contribute to embryonic axes formation. We are investigating the role of physical forces and the external microenvironment for cell polarization, migration, adhesion and cell specification.
Čapek, D., Smutny, M., Tichy, A.M., Morri, M., Janovjak, H. and Heisenberg, C.P., 2019. Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration. Elife, 8, p.e42093.
Smutny M, Ákos Z, Grigolon S, Shamipour S, Ruprecht V, Čapek D, Behrndt M, Papusheva E, Tada M, Hof B, Vicsek T, Salbreux G, Heisenberg CP. Friction forces position the neural anlage. Nat Cell Biol. 2017. doi: 10.1038/ncb3492
Ruprecht V, Wieser S, Callan-Jones A, Smutny M, Morita H, Sako K, Barone V, Ritsch-Marte M, Sixt M, Voituriez R, Heisenberg CP. Cortical Contractility triggers a stochastic switch to fast amoeboid cell motility. Cell. 2015. doi: 10.1016/j.cell.2015.01.008.
Smutny M, Behrndt M, Campinho P, Ruprecht V, Heisenberg CP. UV laser ablation to measure cell and tissue-generated forces in the zebrafish embryo in vivo and ex vivo. Methods Mol Biol. 2015. doi: 10.1007/978-1-4939-1164-6_15.
Smutny M, Cox HL, Leerberg JM, Kovacs EM, Conti MA, Ferguson C, Hamilton NA, Parton RG, Adelstein RS, Yap AS. Myosin II isoforms identify functional modules that support integrity of the epithelial zonula adherens. Nat Cell Biol. 2010. doi: 10.1038/ncb2072.