Differential expression of myogenic regulatory genes and Msx‐1 during dedifferentiation and redifferentiation of regenerating amphibian limbs

Developmental Dynamics - Tập 202 Số 1 - Trang 1-12 - 1995
Hans‐Georg Simon1, Craig Nelson, Deborah J. Goff, Ed Laufer, Bruce Morgan, Clifford J. Tabin
1Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115

Tóm tắt

AbstractAn amputated limb of an adult urodele amphibian is capable of undergoing regeneration. The new structures form from an undifferentiated mass of cells called the regenerative blastema. The cells of the blastema are believed to derive from differentiated tissues of the adult limb. However, the exact source of these cells and the process by which they undergo dedifferentiation are poorly understood. In order to elucidate the molecular and cellular basis for dedifferentiation we isolated a number of genes which are potential regulators of the process. These include Msx1, which is believed to support the undifferentiated and proliferative state of cells in the embryonic limb bud; and two members of the myogenic regulatory gene family, MRF4 and Myf5, which are expressed in differentiated muscle and regulate muscle‐specific gene activity. As anticipated, we find that Msx1 is strongly up‐regulated during the initiation of regeneration. It remains expressed throughout regeneration but is not found in the fully regenerated limb. The myogenic gene MRF4 has the reverse expression pattern. It is expressed in adult limb muscle, is rapidly shut off in early regenerative blastemas, and is only reexpressed at the completion of regeneration. These kinetics are paralleled by those of a musclespecific Myosin gene. In contrast Myf5, a second member of the myogenic gene family, continues to be expressed throughout the regenerative process. Thus, MRF4 and Myf5 are likely to play distinct roles during regeneration. MRF4 may directly regulate muscle phenotype and as such its repression may be a key event in dedifferentiation. Myf5 may play a role in maintaining a distinct myogenic lineage during regeneration. © 1995 Wiley‐Liss, Inc.

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