Marmigère Frédéric, Montelius Andreas, Wegner Michael, Groner Yoram, Reichardt Louis F, Ernfors Patrik
Laboratory of Molecular Neurobiology, Karolinska Institute, MBB, Scheeles väg 1, Stockholm, Sweden.
Nat Neurosci. 2006 Feb;9(2):180-7. doi: 10.1038/nn1631. Epub 2006 Jan 22.
Neural crest cells (NCCs) can adopt different neuronal fates. In NCCs, neurogenin-2 promotes sensory specification but does not specify different subclasses of sensory neurons. Understanding the gene cascades that direct Trk gene activation may reveal mechanisms generating sensory diversity, because different Trks are expressed in different sensory neuron subpopulations. Here we show in chick and mouse that the Runt transcription factor Runx1 promotes axonal growth, is selectively expressed in neural crest-derived TrkA(+) sensory neurons and mediates TrkA transactivation in migratory NCCs. Inhibition of Runt activity depletes TrkA expression and leads to neuronal death. Moreover, Runx1 overexpression is incompatible with multipotency in the migratory neural crest but does not induce expression of pan-neuronal genes. Instead, Runx1-induced neuronal differentiation depends on an existing neurogenin2 proneural gene program. Our data show that Runx1 directs, in a context-dependent manner, key aspects of the establishment of the TrkA(+) nociceptive subclass of neurons.
神经嵴细胞（NCCs）可分化为不同的神经元命运。在神经嵴细胞中，神经生成素-2促进感觉神经元特化，但不能指定感觉神经元的不同亚类。了解指导Trk基因激活的基因级联反应可能揭示产生感觉多样性的机制，因为不同的Trk在不同的感觉神经元亚群中表达。在这里，我们在鸡和小鼠中发现，Runt转录因子Runx1促进轴突生长，在神经嵴衍生的TrkA（+）感觉神经元中选择性表达，并在迁移的神经嵴细胞中介导TrkA反式激活。抑制Runt活性会耗尽TrkA表达并导致神经元死亡。此外，Runx1过表达与迁移神经嵴中的多能性不相容，但不会诱导泛神经元基因的表达。相反，Runx1诱导的神经元分化依赖于现有的神经生成素2神经源性基因程序。我们的数据表明，Runx1以上下文依赖的方式指导TrkA（+）伤害性神经元亚类建立的关键方面。
