Abstract
Vertebrate endoderm development has recently become the focus of intense investigation. In this report, we first show that the zebrafish bonnie and clyde (bon) gene plays a critical early role in endoderm formation. bon mutants exhibit a profound reduction in the number of sox17-expressing endodermal precursors formed during gastrulation, and, consequently, a profound reduction in gut tissue at later stages. The endodermal precursors that do form in bon mutants, however, appear to differentiate normally indicating that bon is not required at later steps of endoderm development. We further demonstrate that bon encodes a paired-class homeodomain protein of the Mix family that is expressed transiently before and during early gastrulation in both mesodermal and endodermal progenitors. Overexpression of bon can rescue endodermal gene expression and the formation of a gut tube in bon mutants. Analysis of a newly identified mutant allele reveals that a single amino acid substitution in the DNA recognition helix of the homeodomain creates a dominant interfering form of Bon when overexpressed. We also show through loss- and gain-of-function analyses that Bon functions exclusively downstream of cyclops and squint signaling. Together, our data demonstrate that Bon is a critical transcriptional regulator of early endoderm formation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Differentiation
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DNA-Binding Proteins*
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Endoderm / cytology*
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Endoderm / metabolism
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Female
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Gastrula / cytology
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Gastrula / metabolism
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Gene Expression Regulation, Developmental
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Genes, Dominant / genetics
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Genes, Suppressor / genetics
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Genetic Linkage / genetics
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High Mobility Group Proteins*
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Homeodomain Proteins / chemistry*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Intracellular Signaling Peptides and Proteins
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Male
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Molecular Sequence Data
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Morphogenesis
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Mutation / genetics
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Nodal Signaling Ligands
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Proteins / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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SOXF Transcription Factors
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Signal Transduction
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Stem Cells / cytology*
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Stem Cells / metabolism
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Transcription Factors*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / physiology
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Xenopus Proteins*
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Zebrafish / abnormalities
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Zebrafish / embryology*
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Zebrafish / genetics*
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Zebrafish Proteins*
Substances
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DNA-Binding Proteins
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High Mobility Group Proteins
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Mix1 protein, Xenopus
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Nodal Signaling Ligands
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Proteins
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RNA, Messenger
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SOXF Transcription Factors
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Transcription Factors
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Transforming Growth Factor beta
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Xenopus Proteins
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Zebrafish Proteins
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ndr1 protein, zebrafish
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ndr2 protein, zebrafish
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nodal1 protein, Xenopus
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sox17 protein, zebrafish
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sox17a protein, Xenopus
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sox17b.1 protein, Xenopus