Wnt/beta-catenin signaling promotes neurogenesis in the diencephalospinal 
dopaminergic system of embryonic zebrafish

Westphal, Markus; Panza, Paolo; Kastenhuber, Edda; Wehrle, Johanna; Driever, Wolfgang

doi:10.1038/s41598-022-04833-8

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Wnt/beta-catenin signaling promotes neurogenesis in the diencephalospinal dopaminergic system of embryonic zebrafish

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Panza, Paolo
Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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引用

Westphal, M., Panza, P., Kastenhuber, E., Wehrle, J., & Driever, W. (2022). Wnt/beta-catenin signaling promotes neurogenesis in the diencephalospinal dopaminergic system of embryonic zebrafish. SCIENTIFIC REPORTS, 12(1):. doi:10.1038/s41598-022-04833-8.

引用: https://hdl.handle.net/21.11116/0000-0009-F617-8

要旨

Wnt/beta-catenin signaling contributes to patterning, proliferation, and differentiation throughout vertebrate neural development. Wnt/beta-catenin signaling is important for mammalian midbrain dopaminergic neurogenesis, while little is known about its role in ventral forebrain dopaminergic development. Here, we focus on the A11-like, Otp-dependent diencephalospinal dopaminergic system in zebrafish. We show that Wnt ligands, receptors and extracellular antagonist genes are expressed in the vicinity of developing Otp-dependent dopaminergic neurons. Using transgenic Wnt/beta-catenin-reporters, we found that Wnt/beta-catenin signaling activity is absent from these dopaminergic neurons, but detected Wnt/beta-catenin activity in cells adjacent to the caudal DC5/6 clusters of Otp-dependent dopaminergic neurons. Pharmacological manipulations of Wnt/beta-catenin signaling activity, as well as heat-shock driven overexpression of Wnt agonists and antagonists, interfere with the development of DC5/6 dopaminergic neurons, such that Wnt/beta-catenin activity positively correlates with their number. Wnt/beta-catenin activity promoted dopaminergic development specifically at stages when DC5/6 dopaminergic progenitors are in a proliferative state. Our data suggest that Wnt/beta-catenin signaling acts in a spatially and temporally restricted manner on proliferative dopaminergic progenitors in the hypothalamus to positively regulate the size of the dopaminergic neuron groups DC5 and DC6.