Mo R, Freer A M, Zinyk D L, Crackower M A, Michaud J, Heng H H, Chik K W, Shi X M, Tsui L C, Cheng S H, Joyner A L, Hui C
Program in Developmental Biology and Division of Endocrinology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Development. 1997 Jan;124(1):113-23. doi: 10.1242/dev.124.1.113.
The correct patterning of vertebrate skeletal elements is controlled by inductive interactions. Two vertebrate hedgehog proteins, Sonic hedgehog and Indian hedgehog, have been implicated in skeletal development. During somite differentiation and limb development, Sonic hedgehog functions as an inductive signal from the notochord, floor plate and zone of polarizing activity. Later in skeletogenesis, Indian hedgehog functions as a regulator of chondrogenesis during endochondral ossification. The vertebrate Gli zinc finger proteins are putative transcription factors that respond to Hedgehog signaling. In Drosophila, the Gli homolog cubitus interruptus is required for the activation of hedgehog targets and also functions as a repressor of hedgehog expression. We show here that Gli2 mutant mice exhibit severe skeletal abnormalities including cleft palate, tooth defects, absence of vertebral body and intervertebral discs, and shortened limbs and sternum. Interestingly, Gli2 and Gli3 (C.-c. Hui and A. L. Joyner (1993). Nature Genet. 3, 241-246) mutant mice exhibit different subsets of skeletal defects indicating that they implement specific functions in the development of the neural crest, somite and lateral plate mesoderm derivatives. Although Gli2 and Gli3 are not functionally equivalent, double mutant analysis indicates that, in addition to their specific roles, they also serve redundant functions during skeletal development. The role of Gli2 and Gli3 in Hedgehog signaling during skeletal development is discussed.
脊椎动物骨骼元件的正确模式形成是由诱导性相互作用控制的。两种脊椎动物刺猬蛋白，即音猬因子（Sonic hedgehog）和印度刺猬蛋白（Indian hedgehog），已被证明与骨骼发育有关。在体节分化和肢体发育过程中，音猬因子作为来自脊索、底板和极化活性区的诱导信号发挥作用。在骨骼发生的后期，印度刺猬蛋白在软骨内骨化过程中作为软骨形成的调节因子发挥作用。脊椎动物Gli锌指蛋白是对刺猬信号作出反应的假定转录因子。在果蝇中，Gli同源物间断翅脉（cubitus interruptus）是激活刺猬靶标的必需因子，并且还作为刺猬蛋白表达的阻遏物发挥作用。我们在此表明，Gli2突变小鼠表现出严重的骨骼异常，包括腭裂、牙齿缺陷、椎体和椎间盘缺失以及四肢和胸骨缩短。有趣的是，Gli2和Gli3（C.-c. Hui和A. L. Joyner（1993年）。《自然遗传学》3，241 - 246）突变小鼠表现出不同的骨骼缺陷子集，表明它们在神经嵴、体节和侧板中胚层衍生物的发育中发挥特定功能。尽管Gli2和Gli3在功能上并不等同，但双突变分析表明，除了它们的特定作用外，它们在骨骼发育过程中也发挥冗余功能。本文讨论了Gli2和Gli3在骨骼发育过程中刺猬信号传导中的作用。
