Open AccessRYK-mediated filopodial pathfinding facilitates midgut elongation
Author(s) -
Sha Wang,
James P Roy,
Abigail J. Tomlinson,
Ellen B Wang,
Yu-Hwai Tsai,
Lisa Cameron,
Julie Underwood,
Jason R. Spence,
Katherine D. Walton,
Steven A. Stacker,
Deborah L. Gumucio,
Terry Lechler
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.195388
Subject(s) - biology , microbiology and biotechnology , pathfinding , anatomy , mitosis , midgut , embryonic stem cell , epithelium , genetics , gene , graph , botany , mathematics , discrete mathematics , shortest path problem , larva
Between embryonic day 10.5 to 14.5, active proliferation drives rapid elongation of the murine midgut epithelial tube. Within this pseudostratified epithelium, nuclei synthesize DNA near the basal surface and move apically to divide. After mitosis, the majority of daughter cells extend a long, basally oriented filopodial protrusion, building a de novo path along which their nuclei can return to the basal side. WNT5A, secreted by surrounding mesenchymal cells, acts as a guidance cue to orchestrate this epithelial pathfinding behavior, but how this signal is received by epithelial cells is unknown. Here, we investigated two known WNT5A receptors, ROR2 and RYK. We found that epithelial ROR2 is dispensable for midgut elongation. However, loss of Ryk phenocopies the Wnt5a−/− phenotype, perturbing post-mitotic pathfinding and leading to apoptosis. These studies reveal that the ligand-receptor pair, WNT5A-RYK, acts as a navigation system to instruct filopodial pathfinding, a process critical for continuous cell cycling to fuel rapid midgut elongation.