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c-Myc Overexpression Increases Cell Size and Impairs Cartilage Differentiation during Chick Limb Development¹

Departamento de Anatomía y Biología Celular (M. E. P., M. A. R.) and Grupo de Biología Molecular del Cáncer, Departamento de Biología Molecular y Unidad Asociada al Centro de Investigaciones Biológicas (CSIC) (M. D. D., J. L.). Universidad de Cantabria, 39011 Santander, Spain.

c-Myc is a transcription factor involved in the control ofcell proliferation, differentiation, and apoptosis, all basicprocesses 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.

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