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BMC Biol. 2015 Apr 11;13:24. doi: 10.1186/s12915-015-0134-4.

Distinct adhesion-independent functions of β-catenin control stage-specific sensory neurogenesis and proliferation.

Author information

1
Cell and Developmental Biology Division, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. max.g@anatom.uzh.ch.
2
Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. tomas.valenta@imls.uzh.ch.
3
Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. patrick.herr@scilifelab.se.
4
Present address: SciLifeLab, Stockholm, Sweden. patrick.herr@scilifelab.se.
5
Cell and Developmental Biology Division, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. lisette.paratore@gmx.ch.
6
Present address: University Hospital Zurich, Clinical Trials Center, Zurich, Switzerland. lisette.paratore@gmx.ch.
7
Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. konrad.basler@imls.uzh.ch.
8
Cell and Developmental Biology Division, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. lukas.sommer@anatom.uzh.ch.

Abstract

BACKGROUND:

β-catenin plays a central role in multiple developmental processes. However, it has been difficult to study its pleiotropic effects, because of the dual capacity of β-catenin to coordinate cadherin-dependent cell adhesion and to act as a component of Wnt signal transduction. To distinguish between the divergent functions of β-catenin during peripheral nervous system development, we made use of a mutant allele of β-catenin that can mediate adhesion but not Wnt-induced TCF transcriptional activation. This allele was combined with various conditional inactivation approaches.

RESULTS:

We show that of all peripheral nervous system structures, only sensory dorsal root ganglia require β-catenin for proper formation and growth. Surprisingly, however, dorsal root ganglia development is independent of cadherin-mediated cell adhesion. Rather, both progenitor cell proliferation and fate specification are controlled by β-catenin signaling. These can be divided into temporally sequential processes, each of which depends on a different function of β-catenin.

CONCLUSIONS:

While early stage proliferation and specific Neurog2- and Krox20-dependent waves of neuronal subtype specification involve activation of TCF transcription, late stage progenitor proliferation and Neurog1-marked sensory neurogenesis are regulated by a function of β-catenin independent of TCF activation and adhesion. Thus, switching modes of β-catenin function are associated with consecutive cell fate specification and stage-specific progenitor proliferation.

PMID:
25885041
PMCID:
PMC4416270
DOI:
10.1186/s12915-015-0134-4
[Indexed for MEDLINE]
Free PMC Article
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