The Tangled Web of Non-Canonical Wnt Signalling in Neural Migration

Abstract

In all multicellular animals, successful embryogenesis is dependent on the ability of cells to detect the status of the local environment and respond appropriately. The nature of the extracellular environment is communicated to the intracellular compartment by ligand/receptor interactions at the cell surface. The Wnt canonical and non-canonical signalling pathways are found in the most primitive metazoans, and they play an essential role in the most fundamental developmental processes in all multicellular organisms. Vertebrates have expanded the number of Wnts and Frizzled receptors and have additionally evolved novel Wnt receptor families (Ryk, Ror). The multiplicity of potential interactions between Wnts, their receptors and downstream effectors has exponentially increased the complexity of the signal transduction network. Signalling through each of the Wnt pathways, as well as crosstalk between them, plays a critical role in the establishment of the complex architecture of the vertebrate central nervous system. In this review, we explore the signalling networks triggered by non-canonical Wnt/receptor interactions, focussing on the emerging roles of the non-conventional Wnt receptors Ryk and Ror. We describe the role of these pathways in neural tube formation and axon guidance where Wnt signalling controls tissue polarity, coordinated cell migration and axon guidance via remodelling of the cytoskeleton.

WNT-C59, a Small-Molecule WNT Inhibitor, Efficiently Induces Anterior Cortex That Includes Cortical Motor Neurons From Human Pluripotent Stem Cells

“…Because C59 inhibits both canonical and noncanonical Wnt signaling, whereas DKK1 and XAV inhibit only canonical signaling, we propose that a noncanonical pathway may play an important role for the induction of anterior cortex, which has been suggested before C59 inhibits the differentiation of neural stem cells to mature neurons [41]. Planar cell polarity (PCP) signaling, a type of noncanonical Wnt signaling, is involved in embryonic morphogenesis and the development of the nervous system by coordinating convergent extension (CE) movements [42,43]. CE movements are characterized by medio-lateral and rostro-caudal movements of cells to narrow and elongate the embryo [43].…”

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

“…Even at the cell surface, noncanonical Wnt signaling is highly variable and complex, with Wnt ligands interacting not only with FZD but also with numerous other receptors, including receptor tyrosine kinase-like orphan receptor (ROR1/2), receptor-like tyrosine kinase (RYK), protein tyrosine kinase 7 (PTK7) and van gogh-like (VANGL1/2) [24]. Adding to this complexity, the Wnt response can differ depending on cell context and on the repertoire of Wnt receptors 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 expressed [25,26], further underlining the importance of determining the "Wnt status" of cells.…”

The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration

“…Derailed is also required for mushroom body development, glomerular patterning, neuromuscular junction formation, synaptogenesis and memory and learning in the fly [20][21][22][23]. These other facets of Ryk function have been comprehensively covered in several recent reviews [24][25][26].…”