Cripps R M, Olson E N
Department of Molecular Biology and Oncology, Hamon Center for Basic Cancer Research, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas, 75235-9148, USA.
Dev Biol. 1998 Nov 1;203(1):106-15. doi: 10.1006/dbio.1998.9040.
The basic helix-loop-helix transcription factor Twist is required for normal development of larval and adult somatic muscles in Drosophila. Adult flies normally have six pairs of dorsal longitudinal indirect flight muscles (DLMs), whereas when Twist function is reduced, only three pairs of DLMs are formed. Although twist is expressed in precursors of adult muscles throughout the larval and early pupal stages, we demonstrate that Twist function is required only during the late larval stage for DLM patterning. In wild-type flies, this is just prior to the time when three pairs of persistent larval muscle fibers split longitudinally to form templates for the six pairs of DLMs. By examining sections at various times during pupal development, we found that splitting of the larval muscles does not occur in twist mutants, indicating that Twist function is required to induce major changes in the larval templates prior to differentiation. The function of Twist in larval muscle splitting is likely mediated by myocyte enhancer factor-2 (MEF2) since in Mef2 hypomorphic mutants splitting is also reduced and Mef2 expression is dependent upon Twist. Our findings define specific roles for Twist and MEF2 during pupal myogenesis and demonstrate that these transcription factors function in adult muscle precursor cells to regulate downstream factors controlling muscle cell splitting and morphogenesis.
果蝇幼虫和成虫体壁肌肉的正常发育需要基本螺旋-环-螺旋转录因子Twist。正常情况下，成年果蝇有六对背纵间接飞行肌（DLM），而当Twist功能减弱时，只形成三对DLM。虽然在整个幼虫期和蛹早期，twist在成年肌肉的前体细胞中表达，但我们证明，Twist功能仅在幼虫后期对DLM模式形成是必需的。在野生型果蝇中，这正好发生在三对残留的幼虫肌纤维纵向分裂形成六对DLM模板之前。通过检查蛹发育过程中不同时间的切片，我们发现幼虫肌肉在twist突变体中不发生分裂，这表明在分化之前，需要Twist功能来诱导幼虫模板发生重大变化。Twist在幼虫肌肉分裂中的功能可能由肌细胞增强因子2（MEF2）介导，因为在Mef2功能减弱的突变体中，分裂也减少，且Mef2表达依赖于Twist。我们的研究结果确定了Twist和MEF2在蛹期肌生成过程中的特定作用，并证明这些转录因子在成年肌肉前体细胞中发挥作用，以调节控制肌肉细胞分裂和形态发生的下游因子。
