The International Journal of Developmental Biology

Int. J. Dev. Biol. 52: 893 - 901 (2008)

Vol 52, Issue 7

Retinoic acid metabolizing factor xCyp26c is specifically expressed in neuroectoderm and regulates anterior neural patterning in Xenopus laevis

Original Article | Published: 1 September 2008

Misaki Tanibe1, Tatsuo Michiue*1,2, Akira Yukita1, Hiroki Danno1, Masayuki Ikuzawa2, Shoichi Ishiura1 and Makoto Asashima*1,2,3

1Graduate School of Arts and Sciences, The University of Tokyo, 2Organ Development Research Laboratory, National Institute of Advanced Industrial Science and Technology (AIST) and 3Organ Regeneration project, International Cooperative Research Program (ICORP), Japan Science and Technology Agency (JST), Japan


Anterior-posterior neural patterning is determined during gastrulation when head structure is induced. Induction of anterior neural structures requires inhibition of Wnt signaling by several Wnt antagonists. We performed microarray analysis to isolate genes regulated by canonical Wnt signaling and abundantly expressed in the anterior neuroectoderm at the early neurula stage. We identified xCyp26c, a Cyp26 (RA-metabolizing protein)-family gene. In situ hybridization showed xCyp26c expression restricted to the anterior region of neurula, while xCyp26a was expressed in both anterior and posterior regions. At the tadpole stage, xCyp26c was also expressed in restricted sets of cranial nerves. Microarray, RT-PCR and in situ hybridization analyses revealed decreased xCyp26c expression with overexpression of b-catenin, suggesting regulation by Wnt/b-catenin signaling. We also assessed the effects of retinoic acid (RA) on xCyp26c expression. Embryos treated with 10-7 M RA showed an anterior shift in the spatial expression of xCyp26c, reflecting a posteriorization effect. Conversely, expression patterns in embryos treated with more than 10-6 M RA were less affected and remained restricted to the most anterior region. Moreover, injection of xCyp26c mRNA into animal poles caused head defects, and exogenous expression of xCyp26c rescued the posteriorizing effect of RA treatment. Taken together, these results implicated a role for xCyp26c in anterior patterning via RA signaling.


Xenopus, retinoic acid, Wnt signaling, AP neural patterning, rhombencephalon

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