Pownall M E, Strunk K E, Emerson C P
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia 19104-6058, USA.
Development. 1996 May;122(5):1475-88. doi: 10.1242/dev.122.5.1475.
Microsurgical, tissue grafting and in situ hybridization techniques have been used to investigate the role of the neural tube and notochord in the control of the myogenic bHLH genes, QmyoD, Qmyf5, Qmyogenin and the cardiac alpha-actin gene, during somite formation in stage 12 quail embryos. Our results reveal that signals from the axial neural tube/notochord complex control both the activation and the maintenance of expression of QmyoD and Qmyf5 in myotomal progenitor cells during the period immediately following somite formation and prior to myotome differentiation. QmyoD and Qmyf5 expression becomes independent of axial signals during myotome differentiation when somites activate expression of Qmyogenin and alpha-actin. Ablation studies reveal that the notochord controls QmyoD activation and the initiation of the transcriptional cascade of myogenic bHLH genes as epithelial somites condense from segmental plate mesoderm. The dorsal medial neural tube then contributes to the maintenance of myogenic bHLH gene expression in newly formed somites. Notochord grafts can activate ectopic QmyoD expression during somite formation, establishing that the notochord is a necessary and sufficient source of diffusible signals to initiate QmyoD expression. Myogenic bHLH gene expression is localized to dorsal medial cells of the somite by inhibitory signals produced by the lateral plate and ventral neural tube. Signaling models for the activation and maintenance of myogenic gene expression and the determination of myotomal muscle in somites are discussed.
已采用显微外科手术、组织移植和原位杂交技术,来研究神经管和脊索在12期鹌鹑胚胎体节形成过程中,对生肌bHLH基因QmyoD、Qmyf5、Qmyogenin以及心脏α-肌动蛋白基因的调控作用。我们的研究结果表明,来自轴旁神经管/脊索复合体的信号,在体节形成后紧接着且在肌节分化之前的这段时间内,控制着肌节祖细胞中QmyoD和Qmyf5表达的激活与维持。当体节激活Qmyogenin和α-肌动蛋白的表达时,在肌节分化过程中,QmyoD和Qmyf5的表达变得独立于轴旁信号。切除研究表明,当上皮性体节从节段板中胚层凝聚时,脊索控制着QmyoD的激活以及生肌bHLH基因转录级联反应的启动。然后,背内侧神经管有助于维持新形成体节中生肌bHLH基因的表达。脊索移植能够在体节形成过程中激活异位的QmyoD表达,这表明脊索是启动QmyoD表达的可扩散信号的必要且充分来源。生肌bHLH基因的表达通过侧板和腹侧神经管产生的抑制性信号,定位于体节的背内侧细胞。本文讨论了生肌基因表达的激活与维持以及体节中肌节肌肉决定的信号模型。