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First published online 10 January 2007
doi: 10.1242/dev.02756

Development 134, 735-746 (2007)
Published by The Company of Biologists 2007
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The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum

Molly K. Nyholm1, Shan-Fu Wu2, Richard I. Dorsky2 and Yevgenya Grinblat1,*

1 Departments of Zoology and Anatomy, University of Wisconsin, Madison, WI, 53706, USA.
2 Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84132, USA.

* Author for correspondence (e-mail: ygrinblat{at}wisc.edu)

Accepted 23 November 2006

Wnt growth factors acting through the canonical intracellular signaling cascade play fundamental roles during vertebrate brain development. In particular, canonical Wnt signaling is crucial for normal development of the dorsal midbrain, the future optic tectum. Wnts act both as patterning signals and as regulators of cell growth. In the developing tectum, Wnt signaling is mitogenic; however, the mechanism of Wnt function is not known. As a step towards better understanding this mechanism, we have identified two new Wnt targets, the closely linked zic2a and zic5 genes. Using a combination of in vivo assays, we show that zic2a and zic5 transcription is activated by Tcf/Lef transcription factors in the dorsal midbrain. Zic2a and Zic5, in turn, have essential, cooperative roles in promoting cell proliferation in the tectum, but lack obvious patterning functions. Collectively these findings suggest that Wnts control midbrain proliferation, at least in part, through regulation of two novel target genes, the zic2a-zic5 gene pair.

Key words: Zic, Wnt, Proliferation, Tectum, Zebrafish






© The Company of Biologists Ltd 2007