@article{6025,
  abstract     = {Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in fz7 mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.},
  author       = {Capek, Daniel and Smutny, Michael and Tichy, Alexandra Madelaine and Morri, Maurizio and Janovjak, Harald L and Heisenberg, Carl-Philipp J},
  journal      = {eLife},
  publisher    = {eLife Sciences Publications},
  title        = {{Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration}},
  doi          = {10.7554/eLife.42093},
  volume       = {8},
  year         = {2019},
}

@phdthesis{50,
  abstract     = {The Wnt/planar cell polarity (Wnt/PCP) pathway determines planar polarity of epithelial cells in both vertebrates and invertebrates. The role that Wnt/PCP signaling plays in mesenchymal contexts, however, is only poorly understood. While previous studies have demonstrated the capacity of Wnt/PCP signaling to polarize and guide directed migration of mesenchymal cells, it remains unclear whether endogenous Wnt/PCP signaling performs these functions instructively, as it does in epithelial cells. Here we developed a light-switchable version of the Wnt/PCP receptor Frizzled 7 (Fz7) to unambiguously distinguish between an instructive and a permissive role of Wnt/PCP signaling for the directional collective migration of mesendoderm progenitor cells during zebrafish gastrulation. We show that prechordal plate (ppl) cell migration is defective in maternal-zygotic fz7a and fz7b (MZ fz7a,b) double mutant embryos, and that Fz7 functions cell-autonomously in this process by promoting ppl cell protrusion formation and directed migration. We further show that local activation of Fz7 can direct ppl cell migration both in vitro and in vivo. Surprisingly, however, uniform Fz7 activation is sufficient to fully rescue the ppl cell migration defect in MZ fz7a,b mutant embryos, indicating that Wnt/PCP signaling functions permissively rather than instructively in directed mesendoderm cell migration during zebrafish gastrulation.},
  author       = {Capek, Daniel},
  issn         = {2663-337X},
  pages        = {95},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Optogenetic Frizzled 7 reveals a permissive function of Wnt/PCP signaling in directed mesenchymal cell migration}},
  doi          = {10.15479/AT:ISTA:TH_1031},
  year         = {2018},
}

@article{676,
  abstract     = {The segregation of different cell types into distinct tissues is a fundamental process in metazoan development. Differences in cell adhesion and cortex tension are commonly thought to drive cell sorting by regulating tissue surface tension (TST). However, the role that differential TST plays in cell segregation within the developing embryo is as yet unclear. Here, we have analyzed the role of differential TST for germ layer progenitor cell segregation during zebrafish gastrulation. Contrary to previous observations that differential TST drives germ layer progenitor cell segregation in vitro, we show that germ layers display indistinguishable TST within the gastrulating embryo, arguing against differential TST driving germ layer progenitor cell segregation in vivo. We further show that the osmolarity of the interstitial fluid (IF) is an important factor that influences germ layer TST in vivo, and that lower osmolarity of the IF compared with standard cell culture medium can explain why germ layers display differential TST in culture but not in vivo. Finally, we show that directed migration of mesendoderm progenitors is required for germ layer progenitor cell segregation and germ layer formation.},
  author       = {Krens, Gabriel and Veldhuis, Jim and Barone, Vanessa and Capek, Daniel and Maître, Jean-Léon and Brodland, Wayne and Heisenberg, Carl-Philipp J},
  issn         = {09501991},
  journal      = {Development},
  number       = {10},
  pages        = {1798 -- 1806},
  publisher    = {Company of Biologists},
  title        = {{Interstitial fluid osmolarity modulates the action of differential tissue surface tension in progenitor cell segregation during gastrulation}},
  doi          = {10.1242/dev.144964},
  volume       = {144},
  year         = {2017},
}

@article{661,
  abstract     = {During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo.},
  author       = {Smutny, Michael and Ákos, Zsuzsa and Grigolon, Silvia and Shamipour, Shayan and Ruprecht, Verena and Capek, Daniel and Behrndt, Martin and Papusheva, Ekaterina and Tada, Masazumi and Hof, Björn and Vicsek, Tamás and Salbreux, Guillaume and Heisenberg, Carl-Philipp J},
  issn         = {14657392},
  journal      = {Nature Cell Biology},
  pages        = {306 -- 317},
  publisher    = {Nature Publishing Group},
  title        = {{Friction forces position the neural anlage}},
  doi          = {10.1038/ncb3492},
  volume       = {19},
  year         = {2017},
}

@article{1100,
  abstract     = {During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation. Endoderm differentiation is suppressed by extended Nodal signaling inducing expression of the transcriptional repressor goosecoid (gsc) in prechordal plate progenitors, which in turn restrains Nodal signaling from upregulating the endoderm differentiation gene sox17 within these cells. Thus, optogenetic manipulation of Nodal signaling identifies a critical role of Nodal signaling duration for organizer cell fate specification during gastrulation.},
  author       = {Sako, Keisuke and Pradhan, Saurabh and Barone, Vanessa and Inglés Prieto, Álvaro and Mueller, Patrick and Ruprecht, Verena and Capek, Daniel and Galande, Sanjeev and Janovjak, Harald L and Heisenberg, Carl-Philipp J},
  journal      = {Cell Reports},
  number       = {3},
  pages        = {866 -- 877},
  publisher    = {Cell Press},
  title        = {{Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation}},
  doi          = {10.1016/j.celrep.2016.06.036},
  volume       = {16},
  year         = {2016},
}

@article{2248,
  abstract     = {Avian forelimb digit homology remains one of the standard themes in comparative biology and EvoDevo research. In order to resolve the apparent contradictions between embryological and paleontological evidence a variety of hypotheses have been presented in recent years. The proposals range from excluding birds from the dinosaur clade, to assignments of homology by different criteria, or even assuming a hexadactyl tetrapod limb ground state. At present two approaches prevail: the frame shift hypothesis and the pyramid reduction hypothesis. While the former postulates a homeotic shift of digit identities, the latter argues for a gradual bilateral reduction of phalanges and digits. Here we present a new model that integrates elements from both hypotheses with the existing experimental and fossil evidence. We start from the main feature common to both earlier concepts, the initiating ontogenetic event: reduction and loss of the anterior-most digit. It is proposed that a concerted mechanism of molecular regulation and developmental mechanics is capable of shifting the boundaries of hoxD expression in embryonic forelimb buds as well as changing the digit phenotypes. Based on a distinction between positional (topological) and compositional (phenotypic) homology criteria, we argue that the identity of the avian digits is II, III, IV, despite a partially altered phenotype. Finally, we introduce an alternative digit reduction scheme that reconciles the current fossil evidence with the presented molecular-morphogenetic model. Our approach identifies specific experiments that allow to test whether gene expression can be shifted and digit phenotypes can be altered by induced digit loss or digit gain.},
  author       = {Capek, Daniel and Metscher, Brian and Müller, Gerd},
  issn         = {15525007},
  journal      = {Journal of Experimental Zoology Part B: Molecular and Developmental Evolution},
  number       = {1},
  pages        = {1 -- 12},
  publisher    = {Wiley-Blackwell},
  title        = {{Thumbs down: A molecular-morphogenetic approach to avian digit homology}},
  doi          = {10.1002/jez.b.22545},
  volume       = {322},
  year         = {2014},
}