Pioneer neurog1 expressing cells ingress into the otic epithelium and instruct neuronal specification

Abstract
Article and author information
Metrics

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 primordium 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.

Article and author information

Author details

Esteban Hoijman

Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain

For correspondence
esteban.hoijman@upf.edu

Competing interests
The authors declare that no competing interests exist.
Laura Fargas

Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain

Competing interests
The authors declare that no competing interests exist.
Patrick Blader

Centre de Biologie du Développement, Université de Toulouse, Toulouse, France

Competing interests
The authors declare that no competing interests exist.
Berta Alsina

Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain

For correspondence
berta.alsina@upf.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6997-1249

Funding

The Ministry of Economy and competitiveness of Spain (BFU2011-270006)

Berta Alsina

The ministry of Economy and Competitiveness of Spain (BFU2014-53203)

Berta Alsina

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments conform to the guidelines from the European Community Directive and the Spanish legislation for the experimental use of animals. The protocols (AR081096P4 and AR081098P3) were approved by the Committee on the Ethics of Animal Experiments of the Parc de Recerca Biomèdica de Barcelona (PRBB), Spain.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.