An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate Journal Article


Author(s): Barone, Vanessa; Lang, Moritz; Krens, Gabriel; Pradhan, Saurabh J; Shami Pour, Shayan; Sako, Keisuke; Sikora, Mateusz; Guet, Cǎlin C; Heisenberg, Carl-Philipp
Article Title: An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate
Affiliation IST Austria
Abstract: Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo.
Keywords: Cell Differentiation; Gastrulation; Zebrafish; gene regulatory network; Cell-cell adhesion; cell-fate specification; Nodal signaling; mesoderm endoderm; kinetic proofreading
Journal Title: Developmental Cell
Volume: 43
Issue 2
ISSN: 1534-5807
Publisher: Cell Press  
Date Published: 2017-10-23
Start Page: 198
End Page: 211
DOI: 10.1016/j.devcel.2017.09.014
Notes: We would like to thank Sanjeev Galande, Akankshi Munjal, Daniel Capek, Jana Slovakova, and Zoltan Spiro for useful comments on previous versions of the manuscript. The research leading to these results has received funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Developmental Cell 43 , 198–211, October 23, 2017 209 Framework Program (FP7/2007–2013) under REA grant agreement no. 291734 to M.L., the CSIR and the DST-BMWF to S.J.P., and the Austrian Science Foundation (FWF) (I 2058-B2) to C.-P.H.
Open access: no