Transcriptional regulation by Pax3 and TGFbeta2 signaling: a potential gene regulatory network in neural crest development.
Pax3 regulates neural crest cell migration and is critical during neural crest development. TGFbs modify neural crest cell migration and differentiation. TGFbeta2 nullizygous embryos (TGFbeta2(-/-)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 TGFbeta2 by directly binding to cis-regulatory elements on its promoter. In this study, we found that the TGFbeta2 nullizygous phenotype can be reversed to the wild type phenotype by down-regulating one allele of Pax3, as in TGFbeta2(-/-)Pax3(+/-) embryos obtained through breeding TGFb2(+/-)Pax3(+/-) mice. The data in this paper suggest that Pax3 and TGFbeta2 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.
Nakazaki
Hiromichi
H
Laboratory of Neural Tube Research, Department of Pediatric Neurosurgery, Childrens Memorial Research Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA.
Shen
Yueh-Wei
YW
Yun
Beth
B
Reddy
Anvesh
A
Khanna
Varun
V
Mania-Farnell
Barbara
B
Ichi
Shunsuke
S
McLone
David G
DG
Tomita
Tadanori
T
Mayanil
C Shekhar K
CS
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics*; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009432:Neural Crest / Q000196:embryology* / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1; D014158:Transcription, Genetic / Q000235:genetics*; D053781:Transforming Growth Factor beta2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D055758:SOX9 Transcription Factor; D000072056:Transcription Factor HES-1; D053781:Transforming Growth Factor beta2; C489734:Hes1 protein, mouse; C102938:Neurog2 protein, mouse; C527933:Sox9 protein, mouse; C068686:Pax3 protein, mouse