Hoxb3 vagal neural crest-specific enhancer element for controlling enteric nervous system development

Authors

  • Kwok Keung Chan,

    1. Department of Biochemistry, The University of Hong Kong, Faculty of Medicine Building, Pokfulam, Hong Kong SAR, China
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    • Drs. Chan and Chen contributed equally to this work.

  • Yuk Shan Chen,

    1. Department of Biochemistry, The University of Hong Kong, Faculty of Medicine Building, Pokfulam, Hong Kong SAR, China
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    • Drs. Chan and Chen contributed equally to this work.

  • Tai On Yau,

    1. Department of Biochemistry, The University of Hong Kong, Faculty of Medicine Building, Pokfulam, Hong Kong SAR, China
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  • Ming Fu,

    1. Department of Surgery, The University of Hong Kong Medical Centre, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
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  • Vincent Chi Hang Lui,

    1. Department of Surgery, The University of Hong Kong Medical Centre, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
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  • Paul Kwong Hang Tam,

    1. Department of Surgery, The University of Hong Kong Medical Centre, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China
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  • Mai Har Sham

    Corresponding author
    1. Department of Biochemistry, The University of Hong Kong, Faculty of Medicine Building, Pokfulam, Hong Kong SAR, China
    • Department of Biochemistry, The University of Hong Kong, 3/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China
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Abstract

The neural and glial cells of the intrinsic ganglia of the enteric nervous system (ENS) are derived from the hindbrain neural crest at the vagal level. The Hoxb3 gene is expressed in the vagal neural crest and in the enteric ganglia of the developing gut during embryogenesis. We have identified a cis-acting enhancer element b3IIIa in the Hoxb3 gene locus. In this study, by transgenic mice analysis, we examined the tissue specificity of the b3IIIa enhancer element using the lacZ reporter gene, with emphasis on the vagal neural crest cells and their derivatives in the developing gut. We found that the b3IIIa-lacZ transgene marks only the vagal region and not the trunk or sacral region. Using cellular markers, we showed that the b3IIIa-lacZ transgene was expressed in a subset of enteric neuroblasts during early development of the gut, and the expression was maintained in differentiated neurons of the myenteric plexus at later stages. The specificity of the b3IIIa enhancer in directing gene expression in the developing ENS was further supported by genetic analysis using the Dom mutant, a spontaneous mouse model of Hirschsprung's disease characterized by the absence of enteric ganglia in the distal gut. The colonization of lacZ-expressing cells in the large intestine was incomplete in all the Dom/b3IIIa-lacZ hybrid mutants we examined. To our knowledge, this is the only vagal neural crest-specific genetic regulatory element identified to date. This element could be used for a variety of genetic manipulations and in establishing transgenic mouse models for studying the development of the ENS. Developmental Dynamics 233:473–483, 2005. © 2005 Wiley-Liss, Inc.

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