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Pax3 is required for enteric ganglia formation and functions with Sox10 to modulate expression of c-ret.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2000 Oct; Vol. 106 (8), pp. 963-71. - Publication Year :
- 2000
-
Abstract
- Hirschsprung disease and Waardenburg syndrome are human genetic diseases characterized by distinct neural crest defects. Patients with Hirschsprung disease suffer from gastrointestinal motility disorders, whereas Waardenburg syndrome consists of defective melanocyte function, deafness, and craniofacial abnormalities. Mutations responsible for Hirschsprung disease and Waardenburg syndrome have been identified, and some patients have been described with characteristics of both disorders. Here, we demonstrate that PAX3, which is often mutated in Waardenburg syndrome, is required for normal enteric ganglia formation. Pax3 can bind to and activate expression of the c-RET gene, which is often mutated in Hirschsprung disease. Pax3 functions with Sox10 to activate transcription of c-RET, and SOX10 mutations result in Waardenburg-Hirschsprung syndrome. Thus, Pax3, Sox10, and c-Ret are components of a neural crest development pathway, and interruption of this pathway at various stages results in neural crest-related human genetic syndromes.
- Subjects :
- Animals
Gene Expression Regulation, Developmental
Hirschsprung Disease genetics
Humans
Mice
Mice, Transgenic
PAX3 Transcription Factor
Paired Box Transcription Factors
Proto-Oncogene Proteins c-ret
SOXE Transcription Factors
Waardenburg Syndrome genetics
DNA-Binding Proteins genetics
Drosophila Proteins
Enteric Nervous System embryology
Ganglia metabolism
High Mobility Group Proteins genetics
Neural Crest embryology
Proto-Oncogene Proteins biosynthesis
Receptor Protein-Tyrosine Kinases biosynthesis
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 106
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 11032856
- Full Text :
- https://doi.org/10.1172/JCI10828