Cytoneme-mediated transport of active Wnt5b/Ror2 complexes in zebrafish
Zhang, C
Date: 14 November 2022
Thesis or dissertation
Publisher
University of Exeter
Degree Title
PhD in Biological Sciences
Abstract
Chemical signalling is the primary means by which cells communicate in embryonic development. The underlying principle refers to a ligand-producing group of cells and a competent receiver group, which can respond to this signal because they express the specific receptor. The Wnt/Planar Cell Polarity (Wnt/PCP) signalling pathway controls ...
Chemical signalling is the primary means by which cells communicate in embryonic development. The underlying principle refers to a ligand-producing group of cells and a competent receiver group, which can respond to this signal because they express the specific receptor. The Wnt/Planar Cell Polarity (Wnt/PCP) signalling pathway controls tissue polarity and cell movement by activating several downstream cascades, including c-Jun N-terminal kinase (JNK) signalling. In the zebrafish embryo, the Wnt/PCP ligand Wnt5b binds to its bona fide receptor Ror2 to trigger the Wnt/PCP signalling cascade. However, it is still unclear how this lipophilic ligand is transported from a localised source through the aqueous extracellular space. This is essential because paracrine Wnt/PCP signalling restructures the embryonic tissue leading to convergence along one axis and extension along the perpendicular axis.
In this thesis, I show that Wnt5b, together with its cognate receptor Ror2, is loaded on signalling filopodia, better known as cytonemes. Wnt5b/Ror2 complex on producing cells can control the emergence of cytoneme and maintain the longer cytonemes. These cytonemes extend several tens of micrometres in the zebrafish gastrula. The Wnt5b/Ror2 complex is handed over from the cytoneme to the receiving cell. The transferred Wnt5b/Ror2 complex remains intact during transport and can trigger Wnt/PCP signalling in the receiving cells, regardless of whether the cell expresses functional receptors. On the tissue level, I further show that cytoneme-dependent spreading of active Wnt5b/Ror2 affects convergence and extension in the zebrafish gastrula. Therefore, I suggest that cytoneme-mediated transfer of ligand-receptor complexes is a vital mechanism for paracrine signalling in a tissue, even if the receiving cells are considered non-responsive by lacking a functional receptor. Thus my work challenges the long-standing concept of characterising responsive and non-responsive tissues based solely on the expression of the receptors.
Doctoral Theses
Doctoral College
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