Dorsoventral patterning of the Xenopus eye: a collaboration of Retinoid, Hedgehog and FGF receptor signaling

Author:

Lupo Giuseppe1,Liu Ying2,Qiu Rong2,Chandraratna Roshantha A. S.3,Barsacchi Giuseppina45,He Rong-Qiao2,Harris William A.1

Affiliation:

1. Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK

2. State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics,Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, PR China

3. Retinoid Research, Departments of Chemistry and Biology, Allergan, Irvine, CA 92623, USA

4. Dipartimento di Fisiologia e Biochimica, Universita' degli Studi di Pisa, Via Carducci 13, 56010 Ghezzano (Pisa), Italy

5. AMBISEN Center, High Technology Center for the Study of Environmental Damage to the Endocrine and Nervous System, Universita' degli Studi di Pisa, Pisa,Italy

Abstract

In the developing spinal cord and telencephalon, ventral patterning involves the interplay of Hedgehog (Hh), Retinoic Acid (RA) and Fibroblast Growth Factor (FGF) signaling. In the eye, ventral specification involves Hh signaling, but the roles of RA and FGF signaling are less clear. By overexpression assays in Xenopus embryos, we found that both RA and FGF receptor (FGFR) signaling ventralize the eye, by expanding optic stalk and ventral retina, and repressing dorsal retina character. Co-overexpression experiments show that RA and FGFR can collaborate with Hh signaling and reinforce its ventralizing activity. In loss-of-function experiments, a strong eye dorsalization was observed after triple inhibition of Hh, RA and FGFR signaling, while weaker effects were obtained by inhibiting only one or two of these pathways. These results suggest that the ventral regionalization of the eye is specified by interactions of Hh, RA and FGFR signaling. We argue that similar mechanisms might control ventral neural patterning throughout the central nervous system.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

Reference54 articles.

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3. Ang, H. L. and Duester, G. (1999b). Stimulation of premature retinoic acid synthesis in Xenopus embryos following premature expression of aldehyde dehydrogenase ALDH1. Eur. J. Biochem.260,227-234.

4. Appel, B. and Eisen, J. S. (2003). Retinoids run rampant: multiple roles during spinal cord and motor neuron development. Neuron40,461-464.

5. Barbieri, A. M., Broccoli, V., Bovolenta, P., Alfano, G.,Marchitiello, A., Mocchetti, C., Crippa, L., Bulfone, A., Marigo, V.,Ballabio, A. et al. (2002). Vax2 inactivation in mouse determines alteration of the eye dorsal-ventral axis, misrouting of the optic fibres and eye coloboma. Development129,805-813.

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