title: Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium.
abstract: The zebrafish posterior lateral line (pLL) is a sensory system that comprises clusters of mechanosensory organs called neuromasts (NMs) that are stereotypically positioned along the surface of the trunk. The NMs are deposited by a migrating pLL primordium, which is organized into polarized rosettes (proto-NMs). During migration, mature proto-NMs are deposited from the trailing part of the primordium, while progenitor cells in the leading part give rise to new proto-NMs. Wnt signaling is active in the leading zone of the primordium and global Wnt inactivation leads to dramatic disorganization of the primordium and a loss of proto-NM formation. However, the exact cellular events that are regulated by the Wnt pathway are not known. We identified a mutant strain, lef1(nl2), that contains a lesion in the Wnt effector gene lef1. lef1(nl2) mutants lack posterior NMs and live imaging reveals that rosette renewal fails during later stages of migration. Surprisingly, the overall primordium patterning, as assayed by the expression of various markers, appears unaltered in lef1(nl2) mutants. Lineage tracing and mosaic analyses revealed that the leading cells (presumptive progenitors) move out of the primordium and are incorporated into NMs; this results in a decrease in the number of proliferating progenitor cells and eventual primordium disorganization. We concluded that Lef1 function is not required for initial primordium organization or migration, but is necessary for proto-NM renewal during later stages of pLL formation. These findings revealed a novel role for the Wnt signaling pathway during mechanosensory organ formation in zebrafish.
authors.affiliation: Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Hillary F
authors.initials: HF
authors.lastname: McGraw
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Drerup
authors.forename: Maya D
authors.initials: MD
authors.lastname: Culbertson
authors.forename: Tor
authors.initials: T
authors.lastname: Linbo
authors.forename: David W
authors.initials: DW
authors.lastname: Raible
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Nechiporuk
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D001846:Bone Development / Q000235:genetics; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian; D053403:Lateral Line System / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C507321:LEF1 protein, zebrafish; C503185:Tcf7 protein, zebrafish; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins