Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene.
Apc is a gene associated with familial adenomatous polyposis coli (FAP) and its inactivation is a critical step in colorectal tumor formation. The protein product, adenomatous polyposis coli (APC), acts to down-regulate intracellular levels of beta-catenin, a key signal transducer in the Wnt signaling. Conditional targeting of Apc in the neural crest of mice caused massive apoptosis of cephalic and cardiac neural crest cells at about 11.5 days post coitum, resulting in craniofacial and cardiac anomalies at birth. Notably, the apoptotic cells localized in the regions where beta-catenin had accumulated. In contrast to its role in colorectal epithelial cells, inactivation of APC leads to dysregulation of beta-catenin/Wnt signaling with resultant apoptosis in certain tissues including neural crest cells.
Hasegawa
Sumitaka
S
Department of Cell Biology, The Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Sato
Tomoyuki
T
Akazawa
Hiroshi
H
Okada
Hitoshi
H
Maeno
Akiteru
A
Ito
Masaki
M
Sugitani
Yoshinobu
Y
Shibata
Hiroyuki
H
Miyazaki Ji
Jun-ichi
J
Katsuki
Motoya
M
Yamauchi
Yasutaka
Y
Yamamura Ki
Ken-ichi
K
Katamine
Shigeru
S
Noda
Tetsuo
T
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D024043:Collagen Type II / Q000378:metabolism; D003106:Colon / Q000196:embryology; D003433:Crosses, Genetic; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005697:Galactosides / Q000378:metabolism; D016158:Genes, p53 / Q000235:genetics; D005838:Genotype; D006321:Heart / Q000196:embryology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology* / Q000473:pathology; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012007:Rectum / Q000196:embryology; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495267:CTNNB1 protein, mouse; D024043:Collagen Type II; D003598:Cytoskeletal Proteins; D005697:Galactosides; D007211:Indoles; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside