XNF-ATc3 affects neural convergent extension.
Convergent extension is the primary driving force elongating the anteroposterior body axis. In Xenopus, convergent extension occurs in the dorsal mesoderm and posterior neural ectoderm, and is mediated by similar molecular pathways within these tissues. In this paper, we show that activation of NF-AT, a transcription factor known to modulate multiple signaling events, inhibits convergent extension in the dorsal mesoderm and in the posterior neural ectoderm. This is seen in whole embryos, mesodermal explants and posterior neural explants, solidly implicating a role of NF-AT in convergent extension. In the whole embryo, inhibition of NF-AT reveals a more selective function, affecting only convergent extension in the neural ectoderm. This specific activity was further teased apart using a variety of temporal and spatial approaches. Targeted injections of dominant-negative XNF-ATc3, or dosing over time with the calcineurin inhibitor cyclosporin in neural tube explants or in whole embryos, shows that inhibition of NF-AT signaling blocks neural convergent extension. Consistent with a function in neural convergent extension, we show that XNF-ATc3 is expressed and transcriptionally active within the neural tube. This work identifies XNF-ATc3 as a regulator of neural convergent extension in Xenopus and adds to a short list of molecules involved in this process.
Department of Genetics, Stanford University Medical School, Stanford, CA 94062, USA.
Annette
A
Borchers
Yuri
Y
Fonar
Dale
D
Frank
Julie C
JC
Baker
D000818:Animals; D019521:Body Patterning; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004475:Ectoderm / Q000166:cytology*; D004625:Embryo, Nonmammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008648:Mesoderm / Q000166:cytology*; D008954:Models, Biological; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009436:Neural Tube Defects / Q000139:chemically induced; D009924:Organ Culture Techniques; D014981:Xenopus / Q000196:embryology / Q000235:genetics; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D050778:NFATC Transcription Factors; C494004:NFATC3 protein, Xenopus; D029867:Xenopus Proteins; D016572:Cyclosporine