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First published online 16 January 2008
doi: 10.1242/dev.012856

Development 135, 677-685 (2008)
Published by The Company of Biologists 2008
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Mechanism of asymmetric ovarian development in chick embryos

Yoshiyasu Ishimaru1,2, Tomoko Komatsu2, Megumi Kasahara1, Yuko Katoh-Fukui2, Hidesato Ogawa2, Yoshiro Toyama3, Mamiko Maekawa3, Kiyotaka Toshimori3, Roshantha A. S. Chandraratna4, Ken-ichirou Morohashi2,*,{ddagger},{dagger} and Hidefumi Yoshioka1,*

1 Department of Natural Sciences, Hyogo University of Teacher Education, 942-1, Shimokume, Kato, Hyogo 673-1494, Japan.
2 Division for Sex Differentiation, National Institute for Basic Biology, National Institutes of Natural Sciences, Myodaijicho, Okazaki, Aichi 444-8787, Japan.
3 Department of Anatomy and Developmental Biology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
4 Retinoid Research, Departments of Chemistry and Biology, Allergan, Irvine, CA 92623, USA.

{dagger} Author for correspondence (e-mail: moro{at}nibb.ac.jp)

Accepted 3 December 2007

In most animals, the gonads develop symmetrically, but most birds develop only a left ovary. A possible role for estrogen in this asymmetric ovarian development has been proposed in the chick, but the mechanism underlying this process is largely unknown. Here, we identify the molecular mechanism responsible for this ovarian asymmetry. Asymmetric PITX2 expression in the left presumptive gonad leads to the asymmetric expression of the retinoic-acid (RA)-synthesizing enzyme, RALDH2, in the right presumptive gonad. Subsequently, RA suppresses expression of the nuclear receptors Ad4BP/SF-1 and estrogen receptor {alpha} in the right ovarian primordium. Ad4BP/SF-1 expressed in the left ovarian primordium asymmetrically upregulates cyclin D1 to stimulate cell proliferation. These data suggest that early asymmetric expression of PITX2 leads to asymmetric ovarian development through up- or downregulation of RALDH2, Ad4BP/SF-1, estrogen receptor {alpha} and cyclin D1.

Key words: Pitx2, Asymmetry, Chick, Estrogen, Ovary






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