Parallel control of mechanosensory hair cell orientation by the PCP and Wnt pathways

Cell polarity plays a crucial role during development of vertebrates and invertebrates. Planar Cell Polarity (PCP) is defined as the coordinated polarity of cells within a tissue axis and is essential for processes such as gastrulation, neural tube closure or hearing. Wnt ligands can be instructive or permissive during PCP-dependent processes, and Wnt pathway mutants are often classified as PCP mutants due to the complexity and the similarities between their phenotypes. Our studies of the zebrafish sensory lateral line reveal that disruptions of the PCP and Wnt pathways have differential effects on hair cell orientations. While mutations in PCP genes cause random orientations of hair cells, mutations in Wnt pathway members induce hair cells to adopt a concentric pattern. We show that PCP signaling is normal in hair cells of Wnt pathway mutants and that the concentric hair cell phenotype is due to altered organization of the surrounding support cells. Thus, the PCP and Wnt pathways work in parallel, as separate pathways to establish proper hair cell orientation. Our data suggest that coordinated support cell organization is established during the formation of lateral line primordia, much earlier than the appearance of hair cells. Together, these finding reveal that hair cell orientation defects are not solely explained by defects in PCP signaling and that some hair cell phenotypes warrant reevaluation

Emergence of Neuronal Diversity during Vertebrate Brain Development

Neurogenesis comprises many highly regulated processes including proliferation, differentiation, and maturation. However, the transcriptional landscapes underlying brain development are poorly characterized. We describe a developmental single-cell catalog of ∼220,000 zebrafish brain cells encompassing 12 stages from embryo to larva. We characterize known and novel gene markers for ∼800 clusters and provide an overview of the diversification of neurons and progenitors across these time points. We also introduce an optimized GESTALT lineage recorder that enables higher expression and recovery of Cas9-edited barcodes to query lineage segregation. Cell type characterization indicates that most embryonic neural progenitor states are transitory and transcriptionally distinct from neural progenitors of post-embryonic stages. Reconstruction of cell specification trajectories reveals that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo. The zebrafish brain development atlas provides a resource to define and manipulate specific subsets of neurons and to uncover the molecular mechanisms underlying vertebrate neurogenesis