The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum.
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.
Nyholm
Molly K
MK
Department of Zoology, University of Wisconsin, Madison, WI 53706, USA.
Wu
Shan-Fu
SF
Dorsky
Richard I
RI
Grinblat
Yevgenya
Y
D000818:Animals; D019521:Body Patterning; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D004625:Embryo, Nonmammalian; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D015398:Signal Transduction; D003336:Tectum Mesencephali / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology
D004268:DNA-Binding Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C493010:Zic5 protein, zebrafish