title: Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord.
abstract: Multiple signaling pathways regulate proliferation and differentiation of neural progenitor cells during early development of the central nervous system (CNS). In the spinal cord, dorsal signaling by bone morphogenic protein (BMP) acts primarily as a patterning signal, while canonical Wnt signaling promotes cell cycle progression in stem and progenitor cells. However, overexpression of Wnt factors or, as shown here, stabilization of the Wnt signaling component beta-catenin has a more prominent effect in the ventral than in the dorsal spinal cord, revealing local differences in signal interpretation. Intriguingly, Wnt signaling is associated with BMP signal activation in the dorsal spinal cord. This points to a spatially restricted interaction between these pathways. Indeed, BMP counteracts proliferation promoted by Wnt in spinal cord neuroepithelial cells. Conversely, Wnt antagonizes BMP-dependent neuronal differentiation. Thus, a mutually inhibitory crosstalk between Wnt and BMP signaling controls the balance between proliferation and differentiation. A model emerges in which dorsal Wnt/BMP signal integration links growth and patterning, thereby maintaining undifferentiated and slow-cycling neural progenitors that form the dorsal confines of the developing spinal cord.
authors.affiliation: Institute of Cell Biology, ETH Zurich, 8093 Zürich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Ille
authors.forename: Suzana
authors.initials: S
authors.lastname: Atanasoski
authors.forename: Sven
authors.initials: S
authors.lastname: Falk
authors.forename: Lars M
authors.initials: LM
authors.lastname: Ittner
authors.forename: David
authors.initials: D
authors.lastname: Märki
authors.forename: Stine
authors.initials: S
authors.lastname: Büchmann-Møller
authors.forename: Heiko
authors.initials: H
authors.lastname: Wurdak
authors.forename: Ueli
authors.initials: U
authors.lastname: Suter
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Lukas
authors.initials: L
authors.lastname: Sommer
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D005697:Galactosides; D007211:Indoles; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D046569:Neuroepithelial Cells / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D005697:Galactosides; D007211:Indoles; D051153:Wnt Proteins; D001973:Bromodeoxyuridine; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside