Delta-like 1 homolog (DLK1) inhibits proliferation and myotube formation of avian QM7 myoblasts

Abstract

Delta-like 1 homolog (DLK1) has been implicated as an important regulator in mammalian muscle development. Our previous studies showed that different alternative splicing isoforms have distinct functions in the regulation of myogenesis in mice. Unlike most mammals, including mice, pigs, cattle, and sheep, DLK1 mRNA for avian species has a single form without alternative splicing. In the current study, we have used QM7 cells, a quail myoblast, to study the role of DLK1 in the regulation of avian myogenesis. Overexpression of DLK1 inhibited myogenesis with a lower fusion rate and thinner myotube compared to the control QM7 cells. Comparison of relative levels of protein and mRNA showed down-regulation of PAX7, MYOG, and MHC, and up-regulation of MYOD by DLK1, suggesting that quail DLK1 inhibits myogenesis at later stages of myogenic differentiation and myotube formation. DLK1 reduced the QM7 cell growth rate which is accompanied by a lower percentage of bromodeoxyuridine positive cells, indicating an inhibitory role of DLK1 in proliferation. During the early post-hatch ages, the relatively slower increase in the amount of total DNA mass in breast muscle of the heavy weight quail line, that has been selected for over 40 generations, could be partially explained by the higher expression of DLK1 compared to the control quail. Taken together, DLK1 inhibits myogenic differentiation and proliferation by regulating the expression levels of myogenic factors in quail. In addition, the regulation of expression level and cleavage of full-length DLK1 may be important factors for regulating myogenesis in quail having no splicing variants of DLK1.

Keywords: DLK1; Delta-like 1 homolog; Myogenesis; QM7; Quail muscle cell.