PMID:19850024

Citation	Abu-Elmagd, M, Robson, L, Sweetman, D, Hadley, J, Francis-West, P and Münsterberg, A (2010) Wnt/Lef1 signaling acts via Pitx2 to regulate somite myogenesis. Dev. Biol. 337:211-9
Abstract	Wnt signaling has been implicated in somite, limb, and branchial arch myogenesis but the mechanisms and roles are not clear. We now show that Wnt signaling via Lef1 acts to regulate the number of premyogenic cells in somites but does not regulate myogenic initiation in the limb bud or maintenance in the first or second branchial arch. We have also analysed the function and regulation of a putative downstream transcriptional target of canonical Wnt signaling, Pitx2. We show that loss-of-function of Pitx2 decreases the number of myogenic cells in the somite, whereas overexpression increases myocyte number particularly in the epaxial region of the myotome. Increased numbers of mitotic cells were observed following overexpression of Pitx2 or an activated form of Lef1, suggesting an effect on cell proliferation. In addition, we show that Pitx2 expression is regulated by canonical Wnt signaling in the epaxial somite and second branchial arch, but not in the limb or the first branchial arch. These results suggest that Wnt/Lef1 signaling regulates epaxial myogenesis via Pitx2 but that this link is uncoupled in other regions of the body, emphasizing the unique molecular networks that control the development of various muscles in vertebrates.
Links	PubMed Online version:10.1016/j.ydbio.2009.10.023
Keywords	Animals; Branchial Region/cytology; Branchial Region/embryology; Branchial Region/metabolism; Cell Count; Cell Differentiation; Cell Proliferation; Chickens; Extremities/embryology; Gene Targeting; Homeodomain Proteins/metabolism; Lymphoid Enhancer-Binding Factor 1/metabolism; Mice; Muscle Development/physiology; Protein Binding; Signal Transduction; Somites/cytology; Somites/embryology; Somites/metabolism; Transcription Factors/metabolism; Wnt Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:DKK1	involved_in	GO:0000122: negative regulation of transcription by RNA polymerase II	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CHICK:PITX2		GO:0008134: transcription factor binding	ECO:0000021:	UniProtKB:O93345	F		Figure 1: Possible interaction is observed between Pitx2 and Lef-1	complete
CHICK:PITX2		GO:0061055: myotome development	ECO:0000315:		P		Figure 2 and 3 show the gene is clearly involved in myotome development.	complete
CHICK:PITX2		GO:0061185: negative regulation of dermatome development	ECO:0000315:		P		Figure 3: Misexpression caused an increased development in the dermatome development suggesting the gene to have a negative effect in vivo.	complete
CHICK:PITX2		GO:0060174: limb bud formation	ECO:0000315:		P		Figure 5 shows clear involvement of Pitx2 in the formation of the limb bud.	complete
CHICK:PITX2	involved_in	GO:2000288: positive regulation of myoblast proliferation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CHICK:PITX2	involved_in	GO:2000287: positive regulation of myotome development	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CHICK:PITX2	involved_in	GO:0061184: positive regulation of dermatome development	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CHICK:PITX2	involved_in	GO:0045944: positive regulation of transcription by RNA polymerase II	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CHICK:PITX2	involved_in	GO:0045663: positive regulation of myoblast differentiation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CHICK:PITX2	involved_in	GO:0030326: embryonic limb morphogenesis	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
CHICK:O93345		GO:0030178: negative regulation of Wnt receptor signaling pathway	ECO:0000315:		P		Figure 1: Negative regulation of Wnt signaling is observed through dominant negative analysis.	complete
CHICK:O93345		GO:0008134: transcription factor binding	ECO:0000021:	UniProtKB:O93385	F		Figure 1: Interaction is observed between Pitx2 and Lef-1 through somitogenesis.	complete
CHICK:O93345		GO:0090244: Wnt receptor signaling pathway involved in somitogenesis	ECO:0000315:		P		Figure 2: Clear involvement of Lef-1 with the Wnt signaling pathway is observed.	complete
CHICK:O93345		GO:0061055: myotome development	ECO:0000315:		P		Figure 2 and 3 show the gene is clearly involved in myotome development.	complete
CHICK:O93345		GO:0061185: negative regulation of dermatome development	ECO:0000315:		P		Figure 3: Misexpression caused an increased development in the dermatome development suggesting the gene to have a negative effect in vivo.	complete

References

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