PMID:15366005

Citation	Riley, BB, Chiang, MY, Storch, EM, Heck, R, Buckles, GR and Lekven, AC (2004) Rhombomere boundaries are Wnt signaling centers that regulate metameric patterning in the zebrafish hindbrain. Dev. Dyn. 231:278-91
Abstract	The vertebrate hindbrain develops from a series of segments (rhombomeres) distributed along the anteroposterior axis. We are studying the roles of Wnt and Delta-Notch signaling in maintaining rhombomere boundaries as organizing centers in the zebrafish hindbrain. Several wnt genes (wnt1, wnt3a, wnt8b, and wnt10b) show elevated expression at rhombomere boundaries, whereas several delta genes (dlA, dlB, and dlD) are expressed in transverse stripes flanking rhombomere boundaries. Partial disruption of Wnt signaling by knockdown of multiple wnt genes, or the Wnt mediator tcf3b, ablates boundaries and associated cell types. Expression of dlA is chaotic, and cell types associated with rhombomere centers are disorganized. Similar patterning defects are observed in segmentation mutants spiel-ohne-grenzen (spg) and valentino (val), which fail to form rhombomere boundaries due to faulty interactions between adjacent rhombomeres. Stripes of wnt expression are variably disrupted, with corresponding disturbances in metameric patterning. Mutations in dlA or mind bomb (mib) disrupt Delta-Notch signaling and cause a wide range of patterning defects in the hindbrain. Stripes of wnt1 are initially normal but subsequently dissipate, and metameric patterning becomes increasingly disorganized. Driving wnt1 expression using a heat-shock construct partially rescues metameric patterning in mib mutants. Thus, rhombomere boundaries act as Wnt signaling centers required for precise metameric patterning, and Delta signals from flanking cells provide feedback to maintain wnt expression at boundaries. Similar feedback mechanisms operate in the Drosophila wing disc and vertebrate limb bud, suggesting coaptation of a conserved signaling module that spatially organizes cells in complex organ systems.
Links	PubMed Online version:10.1002/dvdy.20133
Keywords	Animals; Body Patterning; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Embryonic Structures/anatomy & histology; Embryonic Structures/physiology; Hepatocyte Nuclear Factor 3-beta; In Situ Hybridization; Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/metabolism; Intracellular Signaling Peptides and Proteins; Membrane Proteins/genetics; Membrane Proteins/metabolism; Morphogenesis; Mutation; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Receptors, Notch; Rhombencephalon/anatomy & histology; Rhombencephalon/embryology; Rhombencephalon/physiology; Signal Transduction/physiology; Transcription Factors/genetics; Transcription Factors/metabolism; Wnt Proteins; Wnt1 Protein; Zebrafish; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism
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