Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis.
Previous work has shown that the posteriorising agent retinoic acid can accelerate anterior neuronal differentiation in Xenopus laevis embryos (Papalopulu, N. and Kintner, C. (1996) Development 122, 3409-3418). To elucidate the role of retinoic acid in the primary neurogenesis cascade, we investigated whether retinoic acid treatment of whole embryos could change the spatial expression of a set of genes known to be involved in neurogenesis. We show that retinoic acid expands the N-tubulin, X-ngnr-1, X-MyT1, X-&Dgr;-1 and Gli3 domains and inhibits the expression of Zic2 and sonic hedgehog in the neural ectoderm, whereas a retinoid antagonist produces opposite changes. In contrast, sonic and banded hedgehog overexpression reduced the N-tubulin stripes, enlarged the neural plate at the expense of the neural crest, downregulated Gli3 and upregulated Zic2. Thus, retinoic acid and hedgehog signaling have opposite effects on the prepattern genes Gli3 and Zic2 and on other genes acting downstream in the neurogenesis cascade. In addition, retinoic acid cannot rescue the inhibitory effect of Notch(ICD), Zic2 or sonic hedgehog on primary neurogenesis. Our results suggest that retinoic acid acts very early, upstream of sonic hedgehog, and we propose a model for regulation of differentiation and proliferation in the neural plate, showing that retinoic acid might be activating primary neurogenesis by repressing sonic hedgehog expression.
Franco
P G
PG
Laboratorio de Embriología Molecular, Instituto de Biología Celular y Neurociencias, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121, Buenos Aires, Argentina.
Paganelli
A R
AR
López
S L
SL
Carrasco
A E
AE
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002455:Cell Division; D002839:Chromans / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors; D008636:Mesencephalon / Q000196:embryology; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D009432:Neural Crest / Q000196:embryology; D011506:Proteins / Q000378:metabolism; D012097:Repressor Proteins; D012249:Rhombencephalon / Q000196:embryology; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D014981:Xenopus / Q000196:embryology* / Q000235:genetics*; D029867:Xenopus Proteins; D000074290:Zinc Finger Protein Gli3
D001565:Benzoates; D002839:Chromans; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; C509232:IHH protein, Xenopus; D019476:Insect Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011506:Proteins; D012097:Repressor Proteins; C509239:SHH protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D014404:Tubulin; D029867:Xenopus Proteins; C112757:Zic2 protein, Xenopus; D000074290:Zinc Finger Protein Gli3; C084904:Ro 41-5253; C077245:hh protein, Drosophila; D014212:Tretinoin