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Vertebrate neurogenesis requires inhibition of endogenous bone morphogenetic protein (BMP) signals in the ectoderm. Blocking of BMPs in animal cap explants causes the formation of anterior neural tissues as a default fate. To identify genes involved in the anterior neural specification, we analyzed gene expression profiles using a Xenopus Affymetrix Gene Chip after BMP-4 inhibition in animal cap explants. We found that the xCyp26c gene, encoding a retinoic acid (RA) degradation enzyme, was upregulated following inhibition of BMP signaling in early neuroectodermal cells. Whole-mount in situ hybridization analysis showed that xCyp26c expression started in the anterior region during the early neurula stage. Overexpression of xCyp26c weakly induced neural genes in animal cap explants. xCyp26c abolished the expression of all trans-/cis-RA-induced posterior genes, but not basic FGF-induced posterior genes. Depletion of xCyp26c by morpholino-oligonucleotides suppressed the normal formation of the axis and head, indicating that xCyp26c plays a critical role in the specification of anterior neural tissue in whole embryos. In animal cap explants, however, xCyp26c morpholinos did not alter anterior-to-posterior neural tissue formation. Together, these results suggest that xCyp26c plays a specific role in anterior-posterior (A-P) neural patterning of Xenopus embryos.
Fig. 1. Induction of xCyp26c by blocking BMP in animal cap explants and the expression pattern of xCyp26c in whole embryos. (A) Selection of the ‘Xl.1946.1.A1_at’ gene induced by DNBR in a cDNA microarray. The expression of ‘Xl.1946.1.A1_at’ was confirmed by RT-PCR. (B) Phylogenetic relationships among the xCYP26 proteins. (C) Developmental expression of xCyp26c. RT-PCR analysis was performed at various stages, as indicated (Nieuwkoop and Faber, 1956). Histone 4 or EF1α serve as an RNA loading control. (D) Spatial expression patterns of xCyp26c. Whole-mount in situ hybridization analysis of xCyp26c was performed during oocyte to tail bud stages. Views of whole embryos at the stages are indicated on top of each column. xCyp26c was expressed in the presumptive anterior neural ectoderm, and the expression continued to the tail bud stage.
Fig. 2. Induction of neural genes by overexpression of xCyp26c in animal cap explants. Xenopus embryos at the one cell stage or two-cell stage were injected in the animal pole with xCyp26c mRNA. Animal caps were dissected from the injected embryos at stages 8–9 and cultured to stage 12 (A) or 24 (B). RT-PCR was then performed to detect expression of the indicated genes. EF1α serves as a RNA loading control.
Fig. 3. Inhibition of all-trans and 9-cis retinoic acid-induced posteriorization by overexpression of xCyp26c in animal cap explants. xCyp26c was injected with DNBR, and animal caps were treated with all-trans retinoic acid (AT-RA) (A), 9-cis retinoic acid (9cRA) (B), and basic FGF (bFGF) (C) at stage 8 and then cultured to stage 24. The expression pattern of marker genes were analyzed by RT-PCR.
Fig. 4. Inhibition of normal head and axis formation by depletion of endogenous xCyp26c. Morpholino activity was confirmed by Western blot. (B) Embryos injected with 40 ng of MO-xCyp26c did not have head structures and had short axis formation. (C) xCyp26c was injected with DNBR and animal caps were cultured to stage 24. Expression patterns of Otx2 and HoxB9 were analyzed by RT-PCR.
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