Distribution of neurosensory progenitor pools during inner ear morphogenesis unveiled by cell lineage reconstruction
Abstract
Reconstructing the lineage of cells is central to understanding how the wide diversity of cell types develops. Here, we provide the neurosensory lineage reconstruction of a complex sensory organ, the inner ear, by imaging zebrafish embryos in vivo over an extended timespan, combining cell tracing and cell fate marker expression over time. We deliver the first dynamic map of early neuronal and sensory progenitor pools in the whole otic vesicle. It highlights the remodeling of the neuronal progenitor domain upon neuroblast delamination, and reveals that the order and place of neuroblasts' delamination from the otic epithelium prefigure their position within the SAG. Sensory and non-sensory domains harbor different proliferative activity contributing distinctly to the overall growth of the structure. Therefore, the otic vesicle case exemplifies a generic morphogenetic process where spatial and temporal cues regulate cell fate and functional organization of the rudiment of the definitive organ.
Article and author information
Author details
Funding
Ministerio de Economía y Competitividad (BFU2012-31994)
- Cristina Pujades
Agence Nationale de la Recherche (ANR-10-INBS-04)
- Cristina Pujades
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII3 141918)
- Philipp Germann
Ministerio de Economía y Competitividad (MDM-2014-0370)
- Cristina Pujades
Ministerio de Economía y Competitividad (SEV-2012-0208)
- Philipp Germann
Agence Nationale de la Recherche (ANR-11-EQPX-0029)
- Thierry Savy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Tanya T Whitfield, University of Sheffield, United Kingdom
Ethics
Animal experimentation: This study was performed in strict accordance with the European Regulations. Zebrafish embryos were obtained by mating of adult fish using standard methods. All fish strains were maintained individually as inbred lines. All protocols used have been approved by the Institutional Animal Care and Use Ethic Committee (PRBB-IACUEC), and implemented according to national and European regulations. All experiments were carried out in accordance with the principles of the 3Rs. All our experiments were carried out using the CPC16-008/9125 protocol approved by the Generalitat of Catalonia.
Version history
- Received: October 11, 2016
- Accepted: December 23, 2016
- Accepted Manuscript published: January 4, 2017 (version 1)
- Accepted Manuscript updated: January 12, 2017 (version 2)
- Version of Record published: January 18, 2017 (version 3)
Copyright
© 2017, Dyballa et al.
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.
Metrics
-
- 1,745
- views
-
- 396
- downloads
-
- 20
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Cancer Biology
- Cell Biology
Establishing a zebrafish model of a deadly type of brain tumor highlights the role of the immune system in the early stages of the disease.
-
- Cell Biology
- Neuroscience
One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.