title: Temporal control of neural crest lineage generation by Wnt/β-catenin signaling.
abstract: Wnt/β-catenin signaling controls multiple steps of neural crest development, ranging from neural crest induction, lineage decisions, to differentiation. In mice, conditional β-catenin inactivation in premigratory neural crest cells abolishes both sensory neuron and melanocyte formation. Intriguingly, the generation of melanocytes is also prevented by activation of β-catenin in the premigratory neural crest, which promotes sensory neurogenesis at the expense of other neural crest derivatives. This raises the question of how Wnt/β-catenin signaling regulates the formation of distinct lineages from the neural crest. Using various Cre lines to conditionally activate β-catenin in neural crest cells at different developmental stages, we show that neural crest cell fate decisions in vivo are subject to temporal control by Wnt/β-catenin. Unlike in premigratory neural crest, β-catenin activation in migratory neural crest cells promotes the formation of ectopic melanoblasts, while the production of most other lineages is suppressed. Ectopic melanoblasts emerge at sites of neural crest target structures and in many tissues usually devoid of neural crest-derived cells. β-catenin activation at later stages in glial progenitors or in melanoblasts does not lead to surplus melanoblasts, indicating a narrow time window of Wnt/β-catenin responsiveness during neural crest cell migration. Thus, neural crest cells appear to be multipotent in vivo both before and after emigration from the neural tube but adapt their response to extracellular signals in a temporally controlled manner.
authors.affiliation: Cell and Developmental Biology, Institute of Anatomy, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Lisette
authors.initials: L
authors.lastname: Hari
authors.forename: Iris
authors.initials: I
authors.lastname: Miescher
authors.forename: Olga
authors.initials: O
authors.lastname: Shakhova
authors.forename: Ueli
authors.initials: U
authors.lastname: Suter
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Makoto
authors.initials: M
authors.lastname: Taketo
authors.forename: William D
authors.initials: WD
authors.lastname: Richardson
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Kessaris
authors.forename: Lukas
authors.initials: L
authors.lastname: Sommer
mesh_terms: D000818:Animals; D001287:Attachment Sites, Microbiological; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning; D019070:Cell Lineage; D002465:Cell Movement; D000089622:Doublecortin Domain Proteins; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D019426:Integrases / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000089622:Doublecortin Domain Proteins; D051739:Microphthalmia-Associated Transcription Factor; D008869:Microtubule-Associated Proteins; C497235:Mitf protein, mouse; D009479:Neuropeptides; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases