title: Distinct adhesion-independent functions of β-catenin control stage-specific sensory neurogenesis and proliferation.
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.
authors.affiliation: Cell and Developmental Biology Division, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. max.g@anatom.uzh.ch.
authors.forename: Max Hans-Peter
authors.initials: MH
authors.lastname: Gay
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. tomas.valenta@imls.uzh.ch.
authors.forename: Tomas
authors.initials: T
authors.lastname: Valenta
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. patrick.herr@scilifelab.se.|Present address: SciLifeLab, Stockholm, Sweden. patrick.herr@scilifelab.se.
authors.forename: Patrick
authors.initials: P
authors.lastname: Herr
authors.affiliation: Cell and Developmental Biology Division, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. lisette.paratore@gmx.ch.|Present address: University Hospital Zurich, Clinical Trials Center, Zurich, Switzerland. lisette.paratore@gmx.ch.
authors.forename: Lisette
authors.initials: L
authors.lastname: Paratore-Hari
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. konrad.basler@imls.uzh.ch.
authors.forename: Konrad
authors.initials: K
authors.lastname: Basler
authors.affiliation: Cell and Developmental Biology Division, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. lukas.sommer@anatom.uzh.ch.
authors.forename: Lukas
authors.initials: L
authors.lastname: Sommer
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D019070:Cell Lineage / Q000235:genetics; D002465:Cell Movement; D049109:Cell Proliferation; D005727:Ganglia, Spinal / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009432:Neural Crest / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis; D010641:Phenotype; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000378:metabolism; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051178:alpha Catenin; D051176:beta Catenin