TY - JOUR
T1 - Transcriptional regulation by Pax3 and TGFβ2 signaling
T2 - A potential gene regulatory network in neural crest development
AU - Nakazaki, Hiromichi
AU - Shen, Yueh Wei
AU - Yun, Beth
AU - Reddy, Anvesh
AU - Khanna, Varun
AU - Mania-Farnell, Barbara
AU - Ichi, Shunsuke
AU - McLone, David G.
AU - Tomita, Tadanori
AU - Mayanil, C. Shekhar K.
PY - 2009
Y1 - 2009
N2 - Pax3 regulates neural crest cell migration and is critical during neural crest development. TGFβs modify neural crest cell migration and differentiation. TGFβ2 nullizygous embryos (TGFβ2-/-Pax3+/+) display open neural tube and bifid spine, whereas in wild type embryos the neural tube is closed. In previous work, we have demonstrated that Pax3 regulates TGFβ2 by directly binding to cis -regulatory elements on its promoter. In this study, we found that the TGFβ2 nullizygous phenotype can be reversed to the wild type phenotype by down-regulating one allele of Pax3, as in TGFβ2-/-Pax3+/- embryos obtained through breeding TGFβ2+/-Pax3+/- mice. The data in this paper suggest that Pax3 and TGFβ2 interact in a coordinated gene regulatory network, linked by common downstream effector genes, to bring about this phenotypic reversal. Downstream effectors may include Hes1, Ngn2 and Sox9, as well as other genes involved in neuronal differentiation.
AB - Pax3 regulates neural crest cell migration and is critical during neural crest development. TGFβs modify neural crest cell migration and differentiation. TGFβ2 nullizygous embryos (TGFβ2-/-Pax3+/+) display open neural tube and bifid spine, whereas in wild type embryos the neural tube is closed. In previous work, we have demonstrated that Pax3 regulates TGFβ2 by directly binding to cis -regulatory elements on its promoter. In this study, we found that the TGFβ2 nullizygous phenotype can be reversed to the wild type phenotype by down-regulating one allele of Pax3, as in TGFβ2-/-Pax3+/- embryos obtained through breeding TGFβ2+/-Pax3+/- mice. The data in this paper suggest that Pax3 and TGFβ2 interact in a coordinated gene regulatory network, linked by common downstream effector genes, to bring about this phenotypic reversal. Downstream effectors may include Hes1, Ngn2 and Sox9, as well as other genes involved in neuronal differentiation.
KW - Epithelial-to-mesenchymal transformation
KW - Hes1
KW - Ngn2
KW - Sox9
UR - http://www.scopus.com/inward/record.url?scp=67449124545&partnerID=8YFLogxK
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U2 - 10.1387/ijdb.082682hn
DO - 10.1387/ijdb.082682hn
M3 - Article
C2 - 19123128
AN - SCOPUS:67449124545
SN - 0214-6282
VL - 53
SP - 69
EP - 79
JO - International Journal of Developmental Biology
JF - International Journal of Developmental Biology
IS - 1
ER -