Abstract
Directed neuroblast and neuronal migration is important in the proper development of nervous systems. In C. elegans the bilateral Q neuroblasts QR (on the right) and QL (on the left) undergo an identical pattern of cell division and differentiation but migrate in opposite directions (QR and descendants anteriorly and QL and descendants posteriorly). EGL-20/Wnt, via canonical Wnt signaling, drives the expression of MAB-5/Hox in QL but not QR. MAB-5 acts as a determinant of posterior migration, and mab-5 and egl-20 mutants display anterior QL descendant migrations. Here we analyze the behaviors of QR and QL descendants as they begin their anterior and posterior migrations, and the effects of EGL-20 and MAB-5 on these behaviors. The anterior and posterior daughters of QR (QR.a/p) after the first division immediately polarize and begin anterior migration, whereas QL.a/p remain rounded and non-migratory. After ~1 hour, QL.a migrates posteriorly over QL.p. We find that in egl-20/Wnt, bar-1/β-catenin, and mab-5/Hox mutants, QL.a/p polarize and migrate anteriorly, indicating that these molecules normally inhibit anterior migration of QL.a/p. In egl-20/Wnt mutants, QL.a/p immediately polarize and begin migration, whereas in bar-1/β-catenin and mab-5/Hox, the cells transiently retain a rounded, non-migratory morphology before anterior migration. Thus, EGL-20/Wnt mediates an acute inhibition of anterior migration independently of BAR-1/β-catenin and MAB-5/Hox, and a later, possible transcriptional response mediated by BAR-1/β-catenin and MAB-5/Hox. In addition to inhibiting anterior migration, MAB-5/Hox also cell-autonomously promotes posterior migration of QL.a (and QR.a in a mab-5 gain-of-function).
Highlights
The directed migration of neurons and neuroblasts is important in nervous system development to establish proper connectivity and circuits
In mab-5, QL.a/p transiently retained a rounded, non-migratory morphology, whereas in egl-20, QL.a/p began migration shortly after division, similar to QR.a/p in wildtype. bar-1/β-catenin mutants resembled mab-5 and displayed the transient non-migratory morphology not seen in egl-20. These results suggest that EGL-20 has both an acute MAB-5-independent role and a later MAB-5-dependent role in inhibiting anterior QL.a/p migration, and that the acute role of egl-20 does not involve BAR-1/β-catenin
Genes affected by the mutations were mapped by whole genome single nucleotide polymorphism resequencing using the Cloudmap protocol [20]. Both mapped to a region in the center of LG IV, and each harbored a mutation in the egl-20 gene, which encodes a C. elegans Wnt molecule. egl-20 has been shown previously to affect PQR but not AQR migration [7], consistent with the phenotypes of lq42 and lq74. lq42 introduced a premature stop codon at arginine 296 (C to T), and lq74 was a missense mutation changing cysteine 248 to tyrosine (G to A)
Summary
The directed migration of neurons and neuroblasts is important in nervous system development to establish proper connectivity and circuits. Wnt signaling has been broadly implicated in mammalian cortical and hippocampal neurogenesis [1,2,3]. The Q neuroblasts in C. elegans have been a useful system in which to dissect the molecular mechanisms of directed neuroblast. EGL-20/Wnt and MAB-5/Hox Inhibit Neuronal Migration collection and analysis, decision to publish, or preparation of the manuscript
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