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Publication : Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-beta signaling.

First Author  da Silva S Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  8 Pages  3395-400
PubMed ID  21300867 Mgi Jnum  J:169302
Mgi Id  MGI:4940418 Doi  10.1073/pnas.1014411108
Citation  da Silva S, et al. (2011) Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-{beta} signaling. Proc Natl Acad Sci U S A 108(8):3395-400
abstractText  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.
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