Drs. Chan and Chen contributed equally to this work.
Hoxb3 vagal neural crest-specific enhancer element for controlling enteric nervous system development
Version of Record online: 14 MAR 2005
Copyright © 2005 Wiley-Liss, Inc.
Special Issue: Special Focus on Limb Development
Volume 233, Issue 2, pages 473–483, June 2005
How to Cite
Chan, K. K., Chen, Y. S., Yau, T. O., Fu, M., Lui, V. C. H., Tam, P. K. H. and Sham, M. H. (2005), Hoxb3 vagal neural crest-specific enhancer element for controlling enteric nervous system development. Dev. Dyn., 233: 473–483. doi: 10.1002/dvdy.20347
- Issue online: 12 MAY 2005
- Version of Record online: 14 MAR 2005
- Manuscript Accepted: 14 DEC 2004
- Manuscript Revised: 13 DEC 2004
- Manuscript Received: 15 JUL 2004
- Research Grants Council of Hong Kong SAR, China. Grant Number: HKU 7184/99M
- vagal neural crest;
- enteric nervous system;
- intestinal aganglionosis;
- enhancer element;
- transgenic mice
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.