TY - JOUR
T1 - Ocular and cerebellar defects in zebrafish induced by overexpression of the LIM domains of the Islet-3 LIM/homeodomain protein
AU - Kikuchi, Yutaka
AU - Segawa, Hiroshi
AU - Tokumoto, Mika
AU - Tsubokawa, Tatsuya
AU - Hotta, Yoshiki
AU - Uyemura, Keiichi
AU - Okamoto, Hitoshi
N1 - Funding Information:
We are grateful to Drs. S. Krauss, R. T. Moon, M. Westerfield, D. L. Turner, and G. Eguchi for providing us with the pax2 and pax6 probes, a wnt1 probe, an eng2 probe, a plasmid vector (pCS2), and a monoclonal antibody (2D2B6), respectively; and Drs. R. Ho and N. Hopkins for instruction in blastodermal cell transplantation. We also thank Drs. K. Agata, K. Watanabe, and G. Eguchi for advice; I. B. Dawid, H. Westphal, and their colleagues for discussion; S. W. Wilson, R. Toyama, M. Taira, A. Chiba, and A. Thomson for critical comments; and T. Akiyama, H. Endo, and K. Nakamura for excellent assistance. This research was supported by: Grant-in-Aids and the New Program System from The Ministry of Education, Science, Culture, and Sports of Japan; Special Coordination Funds for Promoting Science and Technology from The Agency of Science and Technology of Japan; and Uehara Foundation. Y. K. received a Fellowship for the Junior Scientists from the Japan Society for the Promotion of Science.
PY - 1997/3
Y1 - 1997/3
N2 - Islet-3 is an LIM/homeodomain protein that is expressed specifically in the eyes and the presumptive tectum in the central nervous system of zebrafish (Danio rerio) embryos. Overexpression of the protein (LIM(Isl-3)) consisting only of the Islet-3 LIM domains in embryos specifically prevented formation of the optic vesicles; caused abnormal termination of the expression of wnt1, engrailed2, and pax2 in the mesencephalic and metencephalic region between 14 hr and 20 hr postfertilization; and severely impaired morphogenetic movement in this region between 20 hr and 26 hr, which should normally lead to formation of the cerebellar primordium. Such defects were all rescued by simultaneous overexpression of Islet-3, suggesting that LIM(Isl-3) acted as a specific dominant-negative variant of Islet-3. These data, combined with the results of mosaic analyses, suggest that Islet-3 is activated by putative LIM-binding cofactors and functions to promote evagination of the optic vesicles and to maintain reciprocal interaction between the mesencephalon and the mesencephalic-metencephalic boundary essential for normal development of this region.
AB - Islet-3 is an LIM/homeodomain protein that is expressed specifically in the eyes and the presumptive tectum in the central nervous system of zebrafish (Danio rerio) embryos. Overexpression of the protein (LIM(Isl-3)) consisting only of the Islet-3 LIM domains in embryos specifically prevented formation of the optic vesicles; caused abnormal termination of the expression of wnt1, engrailed2, and pax2 in the mesencephalic and metencephalic region between 14 hr and 20 hr postfertilization; and severely impaired morphogenetic movement in this region between 20 hr and 26 hr, which should normally lead to formation of the cerebellar primordium. Such defects were all rescued by simultaneous overexpression of Islet-3, suggesting that LIM(Isl-3) acted as a specific dominant-negative variant of Islet-3. These data, combined with the results of mosaic analyses, suggest that Islet-3 is activated by putative LIM-binding cofactors and functions to promote evagination of the optic vesicles and to maintain reciprocal interaction between the mesencephalon and the mesencephalic-metencephalic boundary essential for normal development of this region.
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U2 - 10.1016/S0896-6273(00)81239-8
DO - 10.1016/S0896-6273(00)81239-8
M3 - Article
C2 - 9115732
AN - SCOPUS:0030978508
SN - 0896-6273
VL - 18
SP - 369
EP - 382
JO - Neuron
JF - Neuron
IS - 3
ER -