JAGGED1 Gene Expression During Human Embryogenesis Elucidates the Wide Phenotypic Spectrum of Alagille Syndrome

Mutations of the JAGGED1 gene, encoding a NOTCH receptor ligand, cause Alagille syndrome (AGS), a complex malformative disorder affecting mainly the liver, heart, vertebrae, eye, and face. Minor and occasional features involving kidney, pharynx, systemic arteries, skeleton, and ear are in some cases...

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Published in:Hepatology (Baltimore, Md.) Md.), 2000-09, Vol.32 (3), p.574-581
Main Authors: Crosnier, Cécile, Attié-Bitach, Tania, Encha-Razavi, Férechté, Audollent, Sophie, Soudy, Fardouss, Hadchouel, Michelle, Meunier-Rotival, Michèle, Vekemans, Michel
Format: Article
Language:English
Subjects:
Alagille Syndrome - embryology
Alagille Syndrome - genetics
Biological and medical sciences
Calcium-Binding Proteins
Cardiovascular System - embryology
Digestive system
Digestive System - embryology
Embryo, Mammalian - metabolism
Embryo, Mammalian - physiology
Embryonic and Fetal Development - physiology
Gene Expression
Humans
Intercellular Signaling Peptides and Proteins
Investigative techniques, diagnostic techniques (general aspects)
Jagged-1 Protein
Medical sciences
Membrane Proteins
Nervous System - embryology
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Pharynx - embryology
Phenotype
Proteins - genetics
Respiratory System - embryology
RNA, Messenger - metabolism
Serrate-Jagged Proteins
Urogenital System - embryology
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Summary:Mutations of the JAGGED1 gene, encoding a NOTCH receptor ligand, cause Alagille syndrome (AGS), a complex malformative disorder affecting mainly the liver, heart, vertebrae, eye, and face. Minor and occasional features involving kidney, pharynx, systemic arteries, skeleton, and ear are in some cases associated with the syndrome. To describe the expression of JAGGED1 during human embryogenesis and to study its relationship with all the features of AGS, we performed in situ hybridization studies on human embryos and fetal tissue sections. JAGGED1 was mainly expressed in the cardiovascular system. In the liver,JAGGED1 transcripts were only detected in blood vessels.JAGGED1 was also expressed in other structures of mesenchymal origin (distal mesenchyme of limb buds; mesonephric and metanephric tubules of the kidney) and in epithelial structures including the ciliary margin of the retina and the posterior part of the lens, the ventral epithelium of the otic vesicle, the neurosensory epithelium of the ear vestibule, the epithelium of pharyngeal arches, and the developing central nervous system. The strongJAGGED1 expression during human embryo- and feto-genesis both in the vascular system and in other mesenchymal and epithelial tissues implicates abnormal angiogenesis in the pathogenesis of Alagille syndrome and particularly the paucity of interlobular bile ducts. However, it is probably not the only mechanism of the disease. Except for the central nervous system, there is a strong correlation between JAGGED1 expression and all the features of AGS. This implies that the features occasionally associated with the syndrome are not coincidental. (Hepatology 2000;32:574-581.)
ISSN:0270-9139
1527-3350
DOI:10.1053/jhep.2000.16600