Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-β signaling
Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-β signaling
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DOI：
10.1073/pnas.1014411108
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发表时间：
2011-02-22
影响因子：
11.1
通讯作者：
Wang, Fan
中科院分区：
文献类型：
--
作者：
da Silva, Susana;Hasegawa, Hiroshi;Wang, Fan
哺乳动物躯体感觉拓扑图包含特化的神经元结构，这些结构精确地重现外周感觉器官的空间模式。在小鼠中，触须有序地映射到几个脑干核团上，形成一组被称为“小桶状体”的模块化结构。利用双色离子电渗标记策略，我们发现小桶状体的精确拓扑结构并非神经节内感觉神经元有序位置的结果。接下来我们探索了另一种可能性，即触须图谱的形成受外周来源机制的影响。在外周感觉神经支配期间，几种转化生长因子-β（TGF -β）配体以动态时空模式在触须毛囊中特异性表达。在胚胎晚期通过条件性敲除Smad4来特异性破坏感觉神经元中的TGF -β信号传导，会导致主核和极间核中形成异常的小桶状体，并且在尾核中完全没有小桶状体。我们进一步表明，这种表型并非源于外周神经支配缺陷或中枢轴突生长缺陷，而是由于三叉神经轴突侧支错误投射以及未能正确分离进入合适的小桶状体所致。此外，Smad4缺陷型神经元发育出更简单的终末树突分支并形成更少的突触。总之，我们的研究结果证实了触须来源的TGF -β/Smad4信号传导参与触须躯体感觉定位图的形成。
Mammalian somatosensory topographic maps contain specialized neuronal structures that precisely recapitulate the spatial pattern of peripheral sensory organs. In the mouse, whiskers are orderly mapped onto several brainstem nuclei as a set of modular structures termed barrelettes. Using a dual-color iontophoretic labeling strategy, we found that the precise topography of barrelettes is not a result of ordered positions of sensory neurons within the ganglion. We next explored another possibility that formation of the whisker map is influenced by periphery-derived mechanisms. During the period of peripheral sensory innervation, several TGF-beta ligands are exclusively expressed in whisker follicles in a dynamic spatiotemporal pattern. Disrupting TGF-beta signaling, specifically in sensory neurons by conditional deletion of Smad4 at the late embryonic stage, results in the formation of abnormal barrelettes in the principalis and interpolaris brainstem nuclei and a complete absence of barrelettes in the caudalis nucleus. We further show that this phenotype is not derived from defective peripheral innervation or central axon outgrowth but is attributable to the misprojection and deficient segregation of trigeminal axonal collaterals into proper barrelettes. Furthermore, Smad4-deficient neurons develop simpler terminal arbors and form fewer synapses. Together, our findings substantiate the involvement of whisker-derived TGF-beta/Smad4 signaling in the formation of the whisker somatotopic maps.