Abstract
The zebrafish enteric nervous system (ENS), like those of all other vertebrate species, is principally derived from the vagal neural crest cells (NCC). The developmental controls that govern the migration, proliferation and patterning of the ENS precursors are not well understood. We have investigated the roles of endoderm and Sonic hedgehog (SHH) in the development of the ENS. We show that endoderm is required for the migration of ENS NCC from the vagal region to the anterior end of the intestine. We show that the expression of shh and its receptor ptc-1 correlate with the development of the ENS and demonstrate that hedgehog (HH) signaling is required in two phases, a pre-enteric and an enteric phase, for normal ENS development. We show that HH signaling regulates the proliferation of vagal NCC and ENS precursors in vivo. We also show the zebrafish hand2 is required for the normal development of the intestinal smooth muscle and the ENS. Furthermore we show that endoderm and HH signaling, but not hand2, regulate gdnf expression in the intestine, highlighting a central role of endoderm and SHH in patterning the intestine and the ENS.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Body Patterning
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Cell Movement / physiology
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Endoderm / cytology
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Endoderm / metabolism*
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Enteric Nervous System / cytology
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Enteric Nervous System / embryology*
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Enteric Nervous System / metabolism
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Gene Expression Regulation, Developmental
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Glial Cell Line-Derived Neurotrophic Factor / genetics
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Glial Cell Line-Derived Neurotrophic Factor / metabolism
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Hedgehog Proteins / genetics
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Hedgehog Proteins / metabolism*
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High Mobility Group Proteins / genetics
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High Mobility Group Proteins / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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In Situ Hybridization
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Membrane Proteins
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Mesoderm / cytology
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Mesoderm / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Patched Receptors
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Patched-1 Receptor
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Proto-Oncogene Proteins c-ret / genetics
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Proto-Oncogene Proteins c-ret / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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SOX Transcription Factors
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Signal Transduction / physiology
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Stem Cells / cytology
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Stem Cells / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Veratrum Alkaloids / metabolism
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism*
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Zebrafish* / anatomy & histology
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Zebrafish* / embryology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Glial Cell Line-Derived Neurotrophic Factor
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Hedgehog Proteins
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High Mobility Group Proteins
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Homeodomain Proteins
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Membrane Proteins
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NBPhox protein
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Nerve Tissue Proteins
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Patched Receptors
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Patched-1 Receptor
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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SOX Transcription Factors
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Transcription Factors
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Veratrum Alkaloids
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Zebrafish Proteins
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crestin protein, zebrafish
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hand2 protein, zebrafish
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ptch1 protein, zebrafish
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sox32 protein, zebrafish
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Proto-Oncogene Proteins c-ret
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cyclopamine