Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-β signaling

被引:61
作者
da Silva, Susana [1 ,2 ]
Hasegawa, Hiroshi [1 ]
Scott, Alexandra [1 ]
Zhou, Xiang [1 ]
Wagner, Amanda K. [1 ]
Han, Bao-Xia [1 ]
Wang, Fan [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA
[2] Univ Coimbra, Doctoral Program Expt Biol & Biomed, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal
基金
美国国家卫生研究院;
关键词
SYNAPTIC GROWTH; TRANSCRIPTION FACTOR; RECOMBINASE ACTIVITY; BRAIN-STEM; MOUSE; EXPRESSION; PATTERNS; RAT; ORGANIZATION; VIBRISSAE;
D O I
10.1073/pnas.1014411108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:3395 / 3400
页数:6
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