title: Xenopus Nkx6.3 is a neural plate border specifier required for neural crest development.
abstract: In vertebrates, the neural plate border (NPB) is established by a group of transcription factors including Dlx3, Msx1 and Zic1. The crosstalk between these NPB specifiers governs the separation of the NPB region into placode and neural crest (NC) territories and also their further differentiation. Understanding the mechanisms of NPB formation and NC development is critical for our knowledge of related human diseases. Here we identified Nkx6.3, a transcription factor of the Nkx family, as a new NPB specifier required for neural crest development in Xenopus embryos. XNkx6.3 is expressed in the ectoderm of the neural plate border region at neurula stages, covering the epidermis, placode and neural crest territories, but not the neural plate. Inhibition of Nkx6.3 by dominant negative construct or specific morpholino leads to neural crest defects, while overexpression of Nkx6.3 induces ectopic neural crest in the anterior neural fold. In animal caps, Nkx6.3 alone is able to initiate the whole neural crest regulatory network and induces neural crest fate robustly. We showed that overexpression of Nkx6.3 affects multiple signaling pathways, creating a high-Wnt, low-BMP environment required for neural crest development. Gain- and loss-of-function of Nkx6.3 have compound effects on the expression of known NPB genes, which is largely opposite to that of Dlx3. Overexpression of Dlx3 blocks the NC inducing activity of Nkx6.3. The crosstalk between Nkx6.3, Dlx3 and Msx1 is likely crucial for proper NPB formation and neural crest development in Xenopus.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
authors.forename: Zuming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing, China; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Jiejing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Chaocui
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Mao
mesh_terms: D000818:Animals; D004475:Ectoderm / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D051957:MSX1 Transcription Factor / Q000378:metabolism; D009432:Neural Crest / Q000254:growth & development* / Q000378:metabolism; D054258:Neural Plate / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D014981:Xenopus / Q000254:growth & development* / Q000378:metabolism; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C571370:Dlx3 protein, Xenopus; D051957:MSX1 Transcription Factor; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D051153:Wnt Proteins; D029867:Xenopus Proteins