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PMID:19850024

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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

Significance

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


See also

References

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