TY - JOUR
T1 - Induction of neural crest in Xenopus by transcription factor AP2α
AU - Luo, Ting
AU - Lee, Young Hoon
AU - Saint-Jeannet, Jean Pierre
AU - Sargent, Thomas D.
PY - 2003/1/21
Y1 - 2003/1/21
N2 - We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2α is positively regulated by bone morphogenetic protein (BMP) and Wnt signaling, and that this activation is an essential step in the induction of neural crest (NC). Ectopic expression of AP2α is sufficient to activate high-level expression of NC-specific genes such as Slug and Sox9, which can occur as isolated domains within the neural plate as well as by expansion of endogenous NC territories. AP2α also has the property of inducing NC in isolated ectoderm in which Wnt signaling is provided but BMP signaling is minimized by overexpression of chordin. Like other NC regulatory factors, activation of AP2α requires some attenuation of endogenous BMP signaling; however, this process occurs at a lower threshold for AP2α. Furthermore, AP2α expression domains are larger than for other NC factors. Loss-of-function experiments with antisense AP2α morpholino oligonucleotides result in severe reduction in the NC territory. These results support a central role for AP2α in NC induction. We propose a model in which AP2α expression, along with inactivation of NC inhibitory factors such as Dlx3, establish a feedback loop comprising AP2α, Sox9, and Slug, leading to and maintaining NC specification.
AB - We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2α is positively regulated by bone morphogenetic protein (BMP) and Wnt signaling, and that this activation is an essential step in the induction of neural crest (NC). Ectopic expression of AP2α is sufficient to activate high-level expression of NC-specific genes such as Slug and Sox9, which can occur as isolated domains within the neural plate as well as by expansion of endogenous NC territories. AP2α also has the property of inducing NC in isolated ectoderm in which Wnt signaling is provided but BMP signaling is minimized by overexpression of chordin. Like other NC regulatory factors, activation of AP2α requires some attenuation of endogenous BMP signaling; however, this process occurs at a lower threshold for AP2α. Furthermore, AP2α expression domains are larger than for other NC factors. Loss-of-function experiments with antisense AP2α morpholino oligonucleotides result in severe reduction in the NC territory. These results support a central role for AP2α in NC induction. We propose a model in which AP2α expression, along with inactivation of NC inhibitory factors such as Dlx3, establish a feedback loop comprising AP2α, Sox9, and Slug, leading to and maintaining NC specification.
KW - Bone morphogenetic protein
KW - Morpholino antisense oligonucleotides
KW - Slug
KW - Sox9
KW - Wnt
UR - http://www.scopus.com/inward/record.url?scp=0037458036&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037458036&partnerID=8YFLogxK
U2 - 10.1073/pnas.0237226100
DO - 10.1073/pnas.0237226100
M3 - Article
C2 - 12511599
AN - SCOPUS:0037458036
SN - 0027-8424
VL - 100
SP - 532
EP - 537
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 2
ER -