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Berlin Brandenburg

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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 13 December 2011, Vol.108(50), pp.20018-23
    Description: Taste and most sensory inputs required for the feedback regulation of digestive, respiratory, and cardiovascular organs are conveyed to the central nervous system by so-called "visceral" sensory neurons located in three cranial ganglia (geniculate, petrosal, and nodose) and integrated in the hindbrain by relay sensory neurons located in the nucleus of the solitary tract. Visceral sensory ganglia and the nucleus of the solitary tract all depend for their formation on the pan-visceral homeodomain transcription factor Phox2b, also required in efferent neurons to the viscera. We show here, by genetically tracing Phox2b(+) cells, that in the absence of the protein, many visceral sensory neurons (first- and second-order) survive. However, they adopt a fate--including molecular signature, cell positions, and axonal projections--akin to that of somatic sensory neurons (first- and second-order), located in the trigeminal, superior, and jugular ganglia and the trigeminal sensory nuclei, that convey touch and pain sensation from the oro-facial region. Thus, the cranial sensory pathways, somatic and visceral, are related, and Phox2b serves as a developmental switch from the former to the latter.
    Keywords: Neural Pathways ; Homeodomain Proteins -- Metabolism ; Sensory Receptor Cells -- Metabolism ; Skull -- Metabolism ; Transcription Factors -- Metabolism ; Viscera -- Innervation
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States, Nov 5, 2013, Vol.110(45), p.18174(6)
    Description: During late Schwann cell development, immature Schwann cells segregate large axons from bundles, a process called "axonal radial sorting." Here we demonstrate that canonical Wnt signals play a critical role in radial sorting and assign a role to Wnt and Rspondin ligands in this process. Mice carrying [beta]-catenin loss-of-function mutations show a delay in axonal sorting; conversely, gain-of-function mutations result in accelerated sorting. Sorting deficits are accompanied by abnormal process extension, differentiation, and aberrant cell cycle exit of the Schwann cells. Using primary cultured Schwann cells, we analyze the upstream effectors, Wnt and Rspondin ligands that initiate signaling, and downstream genetic programs that mediate the Wnt response. Our analysis contributes to a better understanding of the mechanisms of Schwann cell development and fate decisions. Axin2-LacZ reporter mice | paracrine mechanism | lamellipodia | myelination | Lgr5 receptor www.pnas.org/cgi/doi/10.1073/pnas.1310490110
    Keywords: Axons -- Physiological Aspects ; Cellular Signal Transduction -- Research ; Neurophysiology -- Research
    ISSN: 0027-8424
    E-ISSN: 10916490
    Source: Cengage Learning, Inc.
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  • 3
    Language: English
    In: Science (New York, N.Y.), 16 March 2012, Vol.335(6074), pp.1373-6
    Description: The sense of touch relies on detection of mechanical stimuli by specialized mechanosensory neurons. The scarcity of molecular data has made it difficult to analyze development of mechanoreceptors and to define the basis of their diversity and function. We show that the transcription factor c-Maf/c-MAF is crucial for mechanosensory function in mice and humans. The development and function of several rapidly adapting mechanoreceptor types are disrupted in c-Maf mutant mice. In particular, Pacinian corpuscles, a type of mechanoreceptor specialized to detect high-frequency vibrations, are severely atrophied. In line with this, sensitivity to high-frequency vibration is reduced in humans carrying a dominant mutation in the c-MAF gene. Thus, our work identifies a key transcription factor specifying development and function of mechanoreceptors and their end organs.
    Keywords: Touch ; Mechanoreceptors -- Cytology ; Proto-Oncogene Proteins C-Maf -- Metabolism
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 4
    Language: English
    In: Developmental Biology, 01 December 2015, Vol.408(1), pp.90-98
    Description: Epithelial progenitor cells of the lung generate all cell types of the mature airway epithelium, among them the neuroendocrine cells. The balance between formation of pulmonary neuroendocrine and non-neuroendocrine cells is controlled by Notch signaling. The Notch target gene is expressed by non-neuroendocrine and absent in neuroendocrine cells. The transcription factor is expressed in a complementary pattern and provides key regulatory information that specifies the neuroendocrine cell fate. The molecular events that occur after the induction of the neuroendocrine differentiation program have received little attention. Here we show that is expressed in pulmonary neuroendocrine cells, and that expression is not initiated in the lung of mutant mice. We use mouse genetics to show that pulmonary neuroendocrine cells depend on for their differentiation. Mutation of blocks terminal differentiation, upregulates Hes1 protein in neuroendocrine cells and interferes with maintenance of expression. We show that Insm1 binds to the promoter and represses , and we propose that the Insm1-dependent repression is required for neuroendocrine development. Our work demonstrates that Insm1 is a key factor regulating differentiation of pulmonary neuroendocrine cells.
    Keywords: Biology ; Zoology
    ISSN: 0012-1606
    E-ISSN: 1095-564X
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  • 5
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 05 November 2013, Vol.110(45), pp.18174-9
    Description: During late Schwann cell development, immature Schwann cells segregate large axons from bundles, a process called "axonal radial sorting." Here we demonstrate that canonical Wnt signals play a critical role in radial sorting and assign a role to Wnt and Rspondin ligands in this process. Mice carrying β-catenin loss-of-function mutations show a delay in axonal sorting; conversely, gain-of-function mutations result in accelerated sorting. Sorting deficits are accompanied by abnormal process extension, differentiation, and aberrant cell cycle exit of the Schwann cells. Using primary cultured Schwann cells, we analyze the upstream effectors, Wnt and Rspondin ligands that initiate signaling, and downstream genetic programs that mediate the Wnt response. Our analysis contributes to a better understanding of the mechanisms of Schwann cell development and fate decisions.
    Keywords: Axin2-Lacz Reporter Mice ; Lgr5 Receptor ; Lamellipodia ; Myelination ; Paracrine Mechanism ; Axons -- Physiology ; Cell Lineage -- Physiology ; Schwann Cells -- Physiology ; Thrombospondins -- Metabolism ; Wnt Signaling Pathway -- Physiology ; Beta Catenin -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 6
    Language: English
    In: Science (New York, N.Y.), 04 July 2014, Vol.345(6192), pp.82-7
    Description: The peripheral autonomic nervous system reaches far throughout the body and includes neurons of diverse functions, such as sympathetic and parasympathetic. We show that the parasympathetic system in mice--including trunk ganglia and the cranial ciliary, pterygopalatine, lingual, submandibular, and otic ganglia--arise from glial cells in nerves, not neural crest cells. The parasympathetic fate is induced in nerve-associated Schwann cell precursors at distal peripheral sites. We used multicolor Cre-reporter lineage tracing to show that most of these neurons arise from bi-potent progenitors that generate both glia and neurons. This nerve origin places cellular elements for generating parasympathetic neurons in diverse tissues and organs, which may enable wiring of the developing parasympathetic nervous system.
    Keywords: Neurogenesis ; Neural Stem Cells -- Cytology ; Neuroglia -- Cytology ; Neurons -- Cytology ; Parasympathetic Nervous System -- Embryology
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 7
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 07 November 2017, Vol.114(45), pp.11980-11985
    Description: Most of the enteric nervous system derives from the "vagal" neural crest, lying at the level of somites 1-7, which invades the digestive tract rostro-caudally from the foregut to the hindgut. Little is known about the initial phase of this colonization, which brings enteric precursors into the foregut. Here we show that the "vagal crest" subsumes two populations of enteric precursors with contrasted origins, initial modes of migration, and destinations. Crest cells adjacent to somites 1 and 2 produce Schwann cell precursors that colonize the vagus nerve, which in turn guides them into the esophagus and stomach. Crest cells adjacent to somites 3-7 belong to the crest streams contributing to sympathetic chains: they migrate ventrally, seed the sympathetic chains, and colonize the entire digestive tract thence. Accordingly, enteric ganglia, like sympathetic ones, are atrophic when deprived of signaling through the tyrosine kinase receptor ErbB3, while half of the esophageal ganglia require, like parasympathetic ones, the nerve-associated form of the ErbB3 ligand, Neuregulin-1. These dependencies might bear relevance to Hirschsprung disease, with which alleles of are associated.
    Keywords: Neuregulin1 ; Chicken ; Enteric Nervous System ; Mouse ; Neural Crest ; Enteric Nervous System -- Cytology ; Ganglia, Sympathetic -- Cytology ; Gastrointestinal Tract -- Embryology ; Neural Crest -- Cytology ; Neuregulin-1 -- Genetics ; Receptor, Erbb-3 -- Genetics ; Schwann Cells -- Cytology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 8
    Article
    Article
    Language: English
    In: Current topics in developmental biology, 2011, Vol.97, pp.xi-xii
    Keywords: Cell Communication -- Physiology ; Signal Transduction -- Physiology
    ISSN: 00702153
    E-ISSN: 1557-8933
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 9
    In: Nature, 1995, Vol.378(6555), p.386
    Description: Neuregulin (also called NDF, heregulin, GGF and ARIA) is a member of the EGF family which induces growth and differentiation of epithelial, glial and muscle cells in culture. The biological effects of the factor are mediated by tyrosine kinase receptors. Neuregulin can bind directly to erbB3 and erbB4 and receptor heterodimerization allows neuregulin-dependent activation of erbB2 (refs 1, 2, 5). A targeted mutation in mice reveals multiple essential roles of neuregulin in development. Here we show that neuregulin -/- embryos die during embryogenesis and display heart malformations. In addition, Schwann cell precursors and cranial ganglia fail to develop normally. The phenotype demonstrates that in vivo neuregulin acts locally and frequently in a paracrine manner. All cell types affected by the mutation express either erbB3 or erbB4, indicating that either of these tyrosine kinase receptors can be a component in recognition and transmission of essential neuregulin signals.
    Keywords: Animals–Physiology ; Cell Differentiation–Physiology ; Cell Line–Cytology ; Embryonic & Fetal Development–Embryology ; Fetal Death–Metabolism ; Ganglia–Genetics ; Ganglia–Physiology ; Ganglia–Embryology ; Glycoproteins–Biosynthesis ; Glycoproteins–Biosynthesis ; Heart–Cytology ; Mice–Metabolism ; Mice, Inbred C57bl–Cytology ; Mutation–Metabolism ; Neuregulins–Metabolism ; Proto-Oncogene Proteins–Metabolism ; Receptor, Epidermal Growth Factor–Metabolism ; Receptor, Erbb-3–Metabolism ; Schwann Cells–Metabolism ; Schwann Cells–Metabolism ; Signal Transduction–Metabolism ; Stem Cells–Metabolism ; Stem Cells–Metabolism ; Proteins ; Prenatal Development ; Heart ; Embryos ; Glycoproteins ; Neuregulins ; Proto-Oncogene Proteins ; Erbb4 Protein ; Receptor, Epidermal Growth Factor ; Receptor, Erbb-3;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 10
    In: Nature, Dec 14, 1995, Vol.378(6558), p.753(1)
    Keywords: Developmental Neurology -- Research
    ISSN: 0028-0836
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