Wnt5a Regulates Ventral Midbrain Morphogenesis and the Development of A9–A10 Dopaminergic Cells In Vivo

• DOI: 10.1371/journal.pone.0003517
• Publication Date: 2008-10-24T17:07:37Z
• Authors: Emma R. Andersson; Nilima Prakash; Lukas Cajanek; Eleonora Minina; Vitezslav Bryja; Lenka Bryjova; Terry P. Yamaguchi; Anita C. Hall; Wolfgang Wurst; Ernest Arenas
• Keywords: rac1 GTP-Binding Protein; Science; Dopamine; Neurogenesis; Models, Biological; Wnt-5a Protein; Mice; 03 medical and health sciences; Mesencephalon; Pregnancy; Morphogenesis; Animals; Cell Proliferation; Mice, Knockout; Neurons; 0303 health sciences; Q; R; Cell Polarity; Cell Differentiation; Embryo, Mammalian; Mice, Inbred C57BL; Wnt Proteins; Medicine; Female; Research Article

Wnt5a is a morphogen that activates the Wnt/planar cell polarity (PCP) pathway and serves multiple functions during development. PCP signaling controls orientation of cells within an epithelial plane as well convergent extension (CE) movements. was previously reported to promote differentiation A9-10 dopaminergic (DA) precursors in vitro. However, mechanism DA function midbrain development vivo remains unclear. We hereby report activated GTPase Rac1 inhibitors blocked Wnt5a-induced neuron ventral (VM) precursor cultures, linking with known effector Wnt/PCP signaling. In vivo, expressed throughout VM at embryonic day (E)9.5, restricted floor basal plate by E11.5-E13.5. Analysis Wnt5a-/- mice revealed transient increase progenitor proliferation E11.5, precociously induced NR4A2+ (Nurr1) pool E12.5. The excess remained undifferentiated until E14.5, when 25% neurons detected. also displayed defect (mid)brain morphogenesis, including impairment elongation rounded ventricular cavity. Interestingly, these alterations affected mostly lineage. Sonic hedgehog-expressing domain broadened flattened, typical CE phenotype, domains occupied Ngn2+ progenitors, TH+ were rostrocaudally reduced laterally expanded. summary, we describe regulation lineage provide evidence for division, precursors.