Abstract
Neural patterning involves regionalised cell specification. Recent studies indicate that cell dynamics play instrumental roles in neural pattern refinement and progression, but the impact of cell behaviour and morphogenesis on neural specification is not understood. Here we combine 4D analysis of cell behaviours with dynamic quantification of proneural expression to uncover the construction of the zebrafish otic neurogenic domain. We identify pioneer cells expressing neurog1 outside the otic epithelium that migrate and ingress into the epithelialising placode to become the first otic neuronal progenitors. Subsequently, neighbouring cells express neurog1 inside the placode, and apical symmetric divisions amplify the specified pool. Interestingly, pioneer cells delaminate shortly after ingression. Ablation experiments reveal that pioneer cells promote neurog1 expression in other otic cells. Finally, ingression relies on the epithelialisation timing controlled by FGF activity. We propose a novel view for otic neurogenesis integrating cell dynamics whereby ingression of pioneer cells instructs neuronal specification.
Highlights
Neural specification relies on proneural genes, which are expressed in specific patterns and underlie the genesis, organisation and the function of the neurons that will subsequently differentiate (Bertrand et al, 2002; Huang et al, 2014)
We have previously identified cell behaviours contributing to otic vesicle morphogenesis (Hoijman et al, 2015) and here we focused on the influence of cell dynamics in the establishment of the neurogenic domain
We imaged in 4D the otic development from stages of otic placode morphogenesis (15 hpf) until neuroblast delamination is abundant and the central lumen is expanding (20.5 hpf, Figure 1A and B; Videos 1 and 2)
Summary
Neural specification relies on proneural genes, which are expressed in specific patterns and underlie the genesis, organisation and the function of the neurons that will subsequently differentiate (Bertrand et al, 2002; Huang et al, 2014). Many signals that pattern the nervous system have been identified. Concomitant with cell specification, neural tissues undergo phases of morphogenesis and/or growth. The contribution of such cell dynamics to neural patterning has been identified. For instance, sharply bordered specification domains involve the sorting of cells along a rough Shh-dependent pattern (Xiong et al, 2013). Differences in the rate of differentiation of cells (which migrate out of the tissue) between distinct domains of the neural tube help to establish the overall pattern during tissue growth (Kicheva et al, 2014). Dynamic spatial rearrangements of cells within a field that is being specified are integrated with patterning mechanisms of positional information by morphogens
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