TY - JOUR
T1 - Genomic, cDNA and embryonic expression analysis of zebrafish IRF6, the gene mutated in the human oral clefting disorders Van der Woude and popliteal pterygium syndromes
AU - Ben, Jin
AU - Jabs, Ethylin Wang
AU - Chong, Samuel S.
N1 - Funding Information:
We thank Yi Zhou (The Children's Hospital Zebrafish Genome Project Initiative, Boston, MA, USA) for performing the RH mapping. Ying Chang (Department of Biological Sciences, National University of Singapore) provided assistance with phylogenetic analyses. Karuna Sampath, Aniket Vilas Gore, Lan Tang and Jing Tian (Temasek Life Science Laboratories, Singapore), and Jinrong Peng and Vladimir Korzh (Institute of Molecular and Cell Biology, Singapore) offered gifts of reagents as well as invaluable suggestions. Yiwen Liu (Tunghai University, Taiwan), Shangwei Chong (Institute of Molecular and Cell Biology, Singapore), Dong Liang, Felicia Cheah, and Sheng Zeng rendered technical assistance. This work was supported by grants from the National University of Singapore Academic Research Fund (R178-000-080-112 and R178-000-104-112).
PY - 2005/6
Y1 - 2005/6
N2 - Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are autosomal dominant clefting disorders recently discovered to be caused by mutations in the IRF6 (Interferon Regulatory Factor 6) gene. The IRF gene family consists of nine members encoding transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-α and -β after viral infection, but the function of IRF6 remains unknown. We have isolated a full-length zebrafish irf6 cDNA, which encodes a 492 amino acid protein that contains a Smad-IRF interaction motif and a DNA-binding domain. The zebrafish irf6 gene consists of eight exons and maps to linkage group 22 closest to marker unp1375. By in situ hybridization analysis of embryo whole-mounts and cryosections, we demonstrate that irf6 is first expressed as a maternal transcript. During gastrulation, irf6 expression was concentrated in the forerunner cells. From the bud stage to the 3-somite stage, irf6 expression was observed in the Kupffer's vesicle. No expression could be detected at the 6-somite and 10-somite stages. At the 14-somite stage, expression was detected in the otic placode. At the 17-somite stage, strong expression was also observed in the cloaca. During the pharyngula, hatch and larva periods up to 5 days post-fertilization, irf6 was expressed in the pharyngeal arches, olfactory and otic placodes, and in the epithelial cells of endoderm derived tissues. The latter tissues include the mouth, pharynx, esophagus, endodermal lining of swim bladder, liver, exocrine pancreas, and associated ducts. Overall, the zebrafish expression data are consistent with the observations of lip pits in VWS patients, as well as more recent reports of alae nasi, otitis media and sensorineural hearing loss documented in some patients.
AB - Van der Woude syndrome (VWS) and popliteal pterygium syndrome (PPS) are autosomal dominant clefting disorders recently discovered to be caused by mutations in the IRF6 (Interferon Regulatory Factor 6) gene. The IRF gene family consists of nine members encoding transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-α and -β after viral infection, but the function of IRF6 remains unknown. We have isolated a full-length zebrafish irf6 cDNA, which encodes a 492 amino acid protein that contains a Smad-IRF interaction motif and a DNA-binding domain. The zebrafish irf6 gene consists of eight exons and maps to linkage group 22 closest to marker unp1375. By in situ hybridization analysis of embryo whole-mounts and cryosections, we demonstrate that irf6 is first expressed as a maternal transcript. During gastrulation, irf6 expression was concentrated in the forerunner cells. From the bud stage to the 3-somite stage, irf6 expression was observed in the Kupffer's vesicle. No expression could be detected at the 6-somite and 10-somite stages. At the 14-somite stage, expression was detected in the otic placode. At the 17-somite stage, strong expression was also observed in the cloaca. During the pharyngula, hatch and larva periods up to 5 days post-fertilization, irf6 was expressed in the pharyngeal arches, olfactory and otic placodes, and in the epithelial cells of endoderm derived tissues. The latter tissues include the mouth, pharynx, esophagus, endodermal lining of swim bladder, liver, exocrine pancreas, and associated ducts. Overall, the zebrafish expression data are consistent with the observations of lip pits in VWS patients, as well as more recent reports of alae nasi, otitis media and sensorineural hearing loss documented in some patients.
KW - IRF6 Interferon Regulatory Factor 6
KW - Popliteal pterygium syndrome
KW - Van der Woude syndrome
KW - Zebrafish
UR - https://www.scopus.com/pages/publications/20444414889
U2 - 10.1016/j.modgep.2005.03.002
DO - 10.1016/j.modgep.2005.03.002
M3 - Article
C2 - 15939375
AN - SCOPUS:20444414889
SN - 1567-133X
VL - 5
SP - 629
EP - 638
JO - Gene Expression Patterns
JF - Gene Expression Patterns
IS - 5
ER -