title: Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-beta signaling.
abstract: 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-β ligands are exclusively expressed in whisker follicles in a dynamic spatiotemporal pattern. Disrupting TGF-β 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-β/Smad4 signaling in the formation of the whisker somatotopic maps.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Susana
authors.initials: S
authors.lastname: da Silva
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Alexandra
authors.initials: A
authors.lastname: Scott
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Wagner
authors.forename: Bao-Xia
authors.initials: BX
authors.lastname: Han
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D001931:Brain Mapping; D001933:Brain Stem / Q000166:cytology*; D051379:Mice; D011984:Sensory Receptor Cells; D015398:Signal Transduction / Q000502:physiology*; D051901:Smad4 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014738:Vibrissae / Q000294:innervation* / Q000502:physiology
chemical_list: D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D016212:Transforming Growth Factor beta