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The chemokine Sdf-1 and its receptor Cxcr4 are required for formation of muscle in zebrafish.

Chong SW, Nguyet LM, Jiang YJ, Korzh V - BMC Dev. Biol. (2007)

Bottom Line: We found that during early myogenesis Sdf1a co-operates with the second Cxcr4 of zebrafish - Cxcr4a resulting in the commitment of myoblast to form fast muscle.Disrupting this chemokine signal caused a reduction in myoD and myf5 expression and fast fiber formation.This demonstrated a role of chemokine signaling during development of skeletal muscles.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Fish Developmental Biology, Institute of Molecular and Cell Biology, Proteos, Singapore. shangwei@imcb.a-star.edu.sg <shangwei@imcb.a-star.edu.sg>

ABSTRACT

Background: During development cell migration takes place prior to differentiation of many cell types. The chemokine receptor Cxcr4 and its ligand Sdf1 are implicated in migration of several cell lineages, including appendicular muscles.

Results: We dissected the role of sdf1-cxcr4 during skeletal myogenesis. We demonstrated that the receptor cxcr4a is expressed in the medial-anterior part of somites, suggesting that chemokine signaling plays a role in this region of the somite. Previous reports emphasized co-operation of Sdf1a and Cxcr4b. We found that during early myogenesis Sdf1a co-operates with the second Cxcr4 of zebrafish - Cxcr4a resulting in the commitment of myoblast to form fast muscle. Disrupting this chemokine signal caused a reduction in myoD and myf5 expression and fast fiber formation. In addition, we showed that a dimerization partner of MyoD and Myf5, E12, positively regulates transcription of cxcr4a and sdf1a in contrast to that of Sonic hedgehog, which inhibited these genes through induction of expression of id2.

Conclusion: We revealed a regulatory feedback mechanism between cxcr4a-sdf1a and genes encoding myogenic regulatory factors, which is involved in differentiation of fast myofibers. This demonstrated a role of chemokine signaling during development of skeletal muscles.

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Slow muscle migration defects in cxcr4a and sdf1a morphants. Confocal images of embryos stained for slow myosin using F59 antibody. Dorsal (A-C;G-I) and lateral (D-F) views of embryonic trunk between the fourth and tenth somites. (A-C) Adaxial cells in cxcr4a and sdf1a morphants are identical to that in controls, 19 h. (D-I) Embryos at 25 h. (D-F) Z-stacked images of ten frames. (G-I) Z-stacked images of two frames. (D) Distinct and properly aligned slow fibers are seen in control embryo. (E,F) Gaps are seen in myotomes of representative cxcr4a and sdf1a morphant, indicated by white arrows. (G) Control. (H,I) Loss of fiber at the superficial layer and misrouted slow muscle, indicated by white arrows in representative cxcr4a and sdf1a morphant respectively. Other misrouted slow fibers in morphants are in different planes (data not shown).
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Figure 4: Slow muscle migration defects in cxcr4a and sdf1a morphants. Confocal images of embryos stained for slow myosin using F59 antibody. Dorsal (A-C;G-I) and lateral (D-F) views of embryonic trunk between the fourth and tenth somites. (A-C) Adaxial cells in cxcr4a and sdf1a morphants are identical to that in controls, 19 h. (D-I) Embryos at 25 h. (D-F) Z-stacked images of ten frames. (G-I) Z-stacked images of two frames. (D) Distinct and properly aligned slow fibers are seen in control embryo. (E,F) Gaps are seen in myotomes of representative cxcr4a and sdf1a morphant, indicated by white arrows. (G) Control. (H,I) Loss of fiber at the superficial layer and misrouted slow muscle, indicated by white arrows in representative cxcr4a and sdf1a morphant respectively. Other misrouted slow fibers in morphants are in different planes (data not shown).

Mentions: It was previously shown that development of slow muscle is closely associated with that of fast muscle and that a change in adhesion within the myotome disrupts migration of slow myoblasts [1]. We tested whether perturbation of either Cxcr4a or Sdf1a affects slow muscle. To eliminate the possibility of early defects in slow myoblasts, we analyzed cxcr4a and sdf1a morphants at 19 hpf, when the posterior adaxial cells have not yet completed their migration. The adaxial cells in both control embryos and morphants (cxcr4a and sdf1a) were adjacent to the notochord (Figures 4A–C). A mild decrease in F59 antibody staining in morphants is presumably due to a slight developmental delay. This correlates with the normal myoD staining in the adaxial cells (see Figures 2A–D). Normally by 25 hpf slow muscle cells migrate to the lateral edge of somite and align to form myofibrils (Figures 4D, G). In cxcr4a and sdf1a morphants this process was affected (Figures 4E–F, H–I). Taken together, these results show that while early specification of slow muscle in both cxcr4a and sdf1a morphants remain normal, the myofibrils were affected.


The chemokine Sdf-1 and its receptor Cxcr4 are required for formation of muscle in zebrafish.

Chong SW, Nguyet LM, Jiang YJ, Korzh V - BMC Dev. Biol. (2007)

Slow muscle migration defects in cxcr4a and sdf1a morphants. Confocal images of embryos stained for slow myosin using F59 antibody. Dorsal (A-C;G-I) and lateral (D-F) views of embryonic trunk between the fourth and tenth somites. (A-C) Adaxial cells in cxcr4a and sdf1a morphants are identical to that in controls, 19 h. (D-I) Embryos at 25 h. (D-F) Z-stacked images of ten frames. (G-I) Z-stacked images of two frames. (D) Distinct and properly aligned slow fibers are seen in control embryo. (E,F) Gaps are seen in myotomes of representative cxcr4a and sdf1a morphant, indicated by white arrows. (G) Control. (H,I) Loss of fiber at the superficial layer and misrouted slow muscle, indicated by white arrows in representative cxcr4a and sdf1a morphant respectively. Other misrouted slow fibers in morphants are in different planes (data not shown).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1904199&req=5

Figure 4: Slow muscle migration defects in cxcr4a and sdf1a morphants. Confocal images of embryos stained for slow myosin using F59 antibody. Dorsal (A-C;G-I) and lateral (D-F) views of embryonic trunk between the fourth and tenth somites. (A-C) Adaxial cells in cxcr4a and sdf1a morphants are identical to that in controls, 19 h. (D-I) Embryos at 25 h. (D-F) Z-stacked images of ten frames. (G-I) Z-stacked images of two frames. (D) Distinct and properly aligned slow fibers are seen in control embryo. (E,F) Gaps are seen in myotomes of representative cxcr4a and sdf1a morphant, indicated by white arrows. (G) Control. (H,I) Loss of fiber at the superficial layer and misrouted slow muscle, indicated by white arrows in representative cxcr4a and sdf1a morphant respectively. Other misrouted slow fibers in morphants are in different planes (data not shown).
Mentions: It was previously shown that development of slow muscle is closely associated with that of fast muscle and that a change in adhesion within the myotome disrupts migration of slow myoblasts [1]. We tested whether perturbation of either Cxcr4a or Sdf1a affects slow muscle. To eliminate the possibility of early defects in slow myoblasts, we analyzed cxcr4a and sdf1a morphants at 19 hpf, when the posterior adaxial cells have not yet completed their migration. The adaxial cells in both control embryos and morphants (cxcr4a and sdf1a) were adjacent to the notochord (Figures 4A–C). A mild decrease in F59 antibody staining in morphants is presumably due to a slight developmental delay. This correlates with the normal myoD staining in the adaxial cells (see Figures 2A–D). Normally by 25 hpf slow muscle cells migrate to the lateral edge of somite and align to form myofibrils (Figures 4D, G). In cxcr4a and sdf1a morphants this process was affected (Figures 4E–F, H–I). Taken together, these results show that while early specification of slow muscle in both cxcr4a and sdf1a morphants remain normal, the myofibrils were affected.

Bottom Line: We found that during early myogenesis Sdf1a co-operates with the second Cxcr4 of zebrafish - Cxcr4a resulting in the commitment of myoblast to form fast muscle.Disrupting this chemokine signal caused a reduction in myoD and myf5 expression and fast fiber formation.This demonstrated a role of chemokine signaling during development of skeletal muscles.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Fish Developmental Biology, Institute of Molecular and Cell Biology, Proteos, Singapore. shangwei@imcb.a-star.edu.sg <shangwei@imcb.a-star.edu.sg>

ABSTRACT

Background: During development cell migration takes place prior to differentiation of many cell types. The chemokine receptor Cxcr4 and its ligand Sdf1 are implicated in migration of several cell lineages, including appendicular muscles.

Results: We dissected the role of sdf1-cxcr4 during skeletal myogenesis. We demonstrated that the receptor cxcr4a is expressed in the medial-anterior part of somites, suggesting that chemokine signaling plays a role in this region of the somite. Previous reports emphasized co-operation of Sdf1a and Cxcr4b. We found that during early myogenesis Sdf1a co-operates with the second Cxcr4 of zebrafish - Cxcr4a resulting in the commitment of myoblast to form fast muscle. Disrupting this chemokine signal caused a reduction in myoD and myf5 expression and fast fiber formation. In addition, we showed that a dimerization partner of MyoD and Myf5, E12, positively regulates transcription of cxcr4a and sdf1a in contrast to that of Sonic hedgehog, which inhibited these genes through induction of expression of id2.

Conclusion: We revealed a regulatory feedback mechanism between cxcr4a-sdf1a and genes encoding myogenic regulatory factors, which is involved in differentiation of fast myofibers. This demonstrated a role of chemokine signaling during development of skeletal muscles.

Show MeSH