Overexpression of Kelch domain containing-2 (mKlhdc2) inhibits differentiation and directed migration of C2C12 myoblasts.
Targeted migration of muscle precursor cells to the anlagen of limb muscles is a complex process, which is only partially understood. We have used Lbx1 mutant mice, which are unable to establish correct migration paths of muscle precursor cells into the limbs to identify new genes involved in the accurate placement of myogenic cells in developing muscles. We found that mKlhdc2 (Kelch domain containing-2), a novel member of the family of Kelch domain containing proteins, is significantly downregulated in Lbx1 homozygous mutant embryos. Functional characterization of mKlhdc2 by targeted overexpression in 10T1/2 fibroblasts and C2C12 muscle cells rendered these cells unable to respond to chemoattractants such as HGF. Furthermore, C2C12 myoblasts overexpressing mKlhdc2 display altered cellular morphology and are unable to differentiate into mature myotubes. Our results suggest that a tightly controlled expression of mKlhdc2 is essential for a faithful execution of the myogenic differentiation and migration program.
Neuhaus
Petra
P
Institute of Physiological Chemistry, MLU Halle-Wittenberg, Hollystr. 1, D-06114 Halle, Germany. petra.neuhaus@kksl.uni-leipzig.de
Jaschinsky
Benjamin
B
Schneider
Sebastian
S
Neuhaus
Herbert
H
Wolter
Annelies
A
Ebelt
Henning
H
Braun
Thomas
T
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002459:Cell Fusion; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D022001:Focal Adhesions / Q000187:drug effects; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects; D009687:Nuclear Proteins; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022502:Stress Fibers / Q000187:drug effects
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C514157:Klhcd2 protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor