Abstract
Barrels in the somatosensory cortex are segregated columns, which somatotopically relate to facial whiskers. The barrel pattern is assumed to be determined by an extrinsic mechanism (the domino theory). This theory is based on whisker lesion experiments and developmental observations regarding the serial establishment of the somatotopic pattern in which pattern formations are relayed from the periphery to the central nervous system. However, the barrel pattern is possibly determined by an intrinsic mechanism, especially in its primitive form. In order to investigate the definitive mechanism, we established an experimental system in which the cortical barrel pattern can be altered, not by using a lesion paradigm, but by epigenetically changing the whisker pattern. Sonic hedgehog (Shh) plays a pivotal role in whisker development. We transfected an adenovirus harboring chicken Shh (Ad-cShh) to mouse embryos (E9.5-E11.5) using an in utero surgical technique. When Ad-cShh was expressed in the epidermis, Bmp4, Ptch, Ptch2 and Gli1 were induced ectopically in the interfollicular region. In contrast, the expression of Bmp2 and Shh itself was unaltered. At a suitable dose of Ad-cShh, some pups displayed supernumerary whiskers or a disordered whisker pattern. The barrel patterns of these mice after the critical period were topographic representations of the contralateral side of the new whisker patterns when visualized by a cytochrome oxidase or Nissle staining method, supporting the instructive role of the extrinsic mechanism.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Afferent Pathways / cytology
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Afferent Pathways / embryology*
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Afferent Pathways / metabolism
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Animals
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Body Patterning / genetics*
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism
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Cell Differentiation / physiology
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Choristoma / genetics
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Fetus
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Gene Expression Regulation, Developmental / genetics*
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Genetic Vectors
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Hedgehog Proteins
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Intracellular Signaling Peptides and Proteins
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Mechanoreceptors / cytology
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Mechanoreceptors / embryology*
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Mechanoreceptors / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism
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Patched Receptors
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Patched-1 Receptor
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Patched-2 Receptor
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Receptors, Cell Surface
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Signal Transduction / physiology
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Somatosensory Cortex / cytology
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Somatosensory Cortex / embryology*
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Somatosensory Cortex / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transforming Growth Factor beta*
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Vibrissae / cytology
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Vibrissae / embryology*
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Vibrissae / metabolism
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Zinc Finger Protein GLI1
Substances
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Bmp2 protein, mouse
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Bmp4 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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Hedgehog Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Oncogene Proteins
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Patched Receptors
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Patched-1 Receptor
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Patched-2 Receptor
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Ptch1 protein, mouse
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Ptch2 protein, mouse
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Receptors, Cell Surface
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Trans-Activators
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Transcription Factors
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Transforming Growth Factor beta
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Zinc Finger Protein GLI1