Limits...
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.

Show MeSH

Related in: MedlinePlus

Formation of fast muscle requires Cxcr4a and Sdf1a. Lateral views (A-F), cross-section (G,H), sagittal section (I,J) and dorsal views. (A) Birefringence revealed by polarized light in cxcr4a (II) and sdf1a (III) morphants was reduced compared to control (I), 30 h. (B) Schematic illustrating black box region used for imaging. Start of yolk sac extension as a guide for the center of frame, indicated by dashed line in diagram of zebrafish embryo. (C-F) Single confocal images taken at level of the somite boundary as a guide of depth. Myosin light chain transgenic line, 51 h. (C,D) mcxcr4a (n = 87/87) and msdf1a (n = 31/35) morphants developed normally. (E,F) In representative cxcr4a (n = 63/71) and sdf1a (n = 73/82) morphants, reduction of GFP signal was observed. (G-J) Transmission electron micrograph of cross (G,H) and sagittal (I,J) sections in trunk region of control and cxcr4a morphants respectively, 36 h. A representative cxcr4a morphant clearly shows a reduction in muscle fibrils. (I,J) Black arrows indicate lack or absence of sarcoplasmic reticulum and muscle fibers in some areas of cxcr4a morphant. For clarity, this region of section (J) was selected where there are at least some muscle fibers. Abbreviations: HM – horizontal myoseptum; ys – yolk sac and yse – yolk sac extension. Scale bars = 500 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1904199&req=5

Figure 3: Formation of fast muscle requires Cxcr4a and Sdf1a. Lateral views (A-F), cross-section (G,H), sagittal section (I,J) and dorsal views. (A) Birefringence revealed by polarized light in cxcr4a (II) and sdf1a (III) morphants was reduced compared to control (I), 30 h. (B) Schematic illustrating black box region used for imaging. Start of yolk sac extension as a guide for the center of frame, indicated by dashed line in diagram of zebrafish embryo. (C-F) Single confocal images taken at level of the somite boundary as a guide of depth. Myosin light chain transgenic line, 51 h. (C,D) mcxcr4a (n = 87/87) and msdf1a (n = 31/35) morphants developed normally. (E,F) In representative cxcr4a (n = 63/71) and sdf1a (n = 73/82) morphants, reduction of GFP signal was observed. (G-J) Transmission electron micrograph of cross (G,H) and sagittal (I,J) sections in trunk region of control and cxcr4a morphants respectively, 36 h. A representative cxcr4a morphant clearly shows a reduction in muscle fibrils. (I,J) Black arrows indicate lack or absence of sarcoplasmic reticulum and muscle fibers in some areas of cxcr4a morphant. For clarity, this region of section (J) was selected where there are at least some muscle fibers. Abbreviations: HM – horizontal myoseptum; ys – yolk sac and yse – yolk sac extension. Scale bars = 500 nm.

Mentions: We then analyzed cxcr4a and sdf1a morphants in more details. Both cxcr4a and sdf1a morphants have reduced birefringency in myotomes (Figure 3A). In addition, transgenic mylz2-GFP morphants of cxcr4a and sdf1a show reduced GFP expression (Figures 3B–F). This prompted us to check the ultrastructure of muscle fibers in morphants using transmission electron microscopy (TEM). Both cross and sagittal sections illustrated that myofibrils were reduced in cxcr4a morphants (Figures 3G–J). Taken together, these results indicated that deficiency in Sdf1a-Cxcr4a mediated signaling caused abnormal development of skeletal muscles. The affected somitic cells most likely remained undifferentiated.


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)

Formation of fast muscle requires Cxcr4a and Sdf1a. Lateral views (A-F), cross-section (G,H), sagittal section (I,J) and dorsal views. (A) Birefringence revealed by polarized light in cxcr4a (II) and sdf1a (III) morphants was reduced compared to control (I), 30 h. (B) Schematic illustrating black box region used for imaging. Start of yolk sac extension as a guide for the center of frame, indicated by dashed line in diagram of zebrafish embryo. (C-F) Single confocal images taken at level of the somite boundary as a guide of depth. Myosin light chain transgenic line, 51 h. (C,D) mcxcr4a (n = 87/87) and msdf1a (n = 31/35) morphants developed normally. (E,F) In representative cxcr4a (n = 63/71) and sdf1a (n = 73/82) morphants, reduction of GFP signal was observed. (G-J) Transmission electron micrograph of cross (G,H) and sagittal (I,J) sections in trunk region of control and cxcr4a morphants respectively, 36 h. A representative cxcr4a morphant clearly shows a reduction in muscle fibrils. (I,J) Black arrows indicate lack or absence of sarcoplasmic reticulum and muscle fibers in some areas of cxcr4a morphant. For clarity, this region of section (J) was selected where there are at least some muscle fibers. Abbreviations: HM – horizontal myoseptum; ys – yolk sac and yse – yolk sac extension. Scale bars = 500 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Formation of fast muscle requires Cxcr4a and Sdf1a. Lateral views (A-F), cross-section (G,H), sagittal section (I,J) and dorsal views. (A) Birefringence revealed by polarized light in cxcr4a (II) and sdf1a (III) morphants was reduced compared to control (I), 30 h. (B) Schematic illustrating black box region used for imaging. Start of yolk sac extension as a guide for the center of frame, indicated by dashed line in diagram of zebrafish embryo. (C-F) Single confocal images taken at level of the somite boundary as a guide of depth. Myosin light chain transgenic line, 51 h. (C,D) mcxcr4a (n = 87/87) and msdf1a (n = 31/35) morphants developed normally. (E,F) In representative cxcr4a (n = 63/71) and sdf1a (n = 73/82) morphants, reduction of GFP signal was observed. (G-J) Transmission electron micrograph of cross (G,H) and sagittal (I,J) sections in trunk region of control and cxcr4a morphants respectively, 36 h. A representative cxcr4a morphant clearly shows a reduction in muscle fibrils. (I,J) Black arrows indicate lack or absence of sarcoplasmic reticulum and muscle fibers in some areas of cxcr4a morphant. For clarity, this region of section (J) was selected where there are at least some muscle fibers. Abbreviations: HM – horizontal myoseptum; ys – yolk sac and yse – yolk sac extension. Scale bars = 500 nm.
Mentions: We then analyzed cxcr4a and sdf1a morphants in more details. Both cxcr4a and sdf1a morphants have reduced birefringency in myotomes (Figure 3A). In addition, transgenic mylz2-GFP morphants of cxcr4a and sdf1a show reduced GFP expression (Figures 3B–F). This prompted us to check the ultrastructure of muscle fibers in morphants using transmission electron microscopy (TEM). Both cross and sagittal sections illustrated that myofibrils were reduced in cxcr4a morphants (Figures 3G–J). Taken together, these results indicated that deficiency in Sdf1a-Cxcr4a mediated signaling caused abnormal development of skeletal muscles. The affected somitic cells most likely remained undifferentiated.

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
Related in: MedlinePlus