c-Myc overexpression increases cell size and impairs cartilage differentiation during chick limb development.
c-Myc is a transcription factor involved in the control of cell proliferation, differentiation, and apoptosis, all basic processes for embryogenesis. To analyze c-Myc roles in limb development, we overexpressed c-myc in chick embryos using a retroviral vector. Forced c-myc expression resulted in enlarged limbs, because of an increase in cell size not accompanied by modifications in cell proliferation. However, at later stages, limbs overexpressing c-myc showed a marked shortening of their skeletal elements, because of the inhibition of chondrocyte maturation. c-Myc interfered with chondrogenesis, independently of the Indian hedgehog/parathyroid hormone-related protein and Wnt5a/Wnt5b regulatory loops. c-myc-infected limbs also exhibited patterning defects, such as extra-phalangeal elements and delayed interdigital apoptosis that occasionally led to interdigital chondrogenesis. In contrast, c-myc overexpression did not interfere with other processes, such as muscle differentiation. Although based on overexpression experiments, our results suggest that endogenous c-Myc may be implicated in the control of cell size and skeletal differentiation during normal limb development.
Piedra
M Elisa
ME
Departamento de Anatomía y Biología Celular, Universidad de Cantabria, 39011 Santander, Spain.
Delgado
M Dolores
MD
Ros
Maria A
MA
León
Javier
J
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002356:Cartilage / Q000166:cytology* / Q000196:embryology / Q000648:ultrastructure; D002454:Cell Differentiation; D002455:Cell Division; D002642:Chick Embryo; D019902:Chondrocytes / Q000166:cytology; D005121:Extremities / Q000196:embryology*; D005434:Flow Cytometry; D016259:Genes, myc; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D009132:Muscles / Q000166:cytology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D001973:Bromodeoxyuridine