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S. Kanakubo, T. Nomura, M. Tamai, K. Nishida, N. Osumi; Abnormal Migration and Distribution of Neural Crest Cells in Pax6 Heterozygous Mutant Eye, a Model for Human Eye Diseases . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5628.
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© ARVO (1962-2015); The Authors (2016-present)
PAX6/Pax6 gene encodes a transcription factor that is crucially required for eye development. Pax6 heterozygous mutant mouse (Pax6Sey/+) shows various ocular anomalies corresponding to human eye diseases. Neural crest cells (NCCs) contribute to a large part of ocular tissues, although the role of Pax6 on NCCs in the ocular region has not been well known. Here we report the results of comprehensive phenotype analyses of Pax6Sey/+ mutant eyes focusing on the contribution of NCCs from the early developing stages.
Transgenic mice expressing Cre enzyme driven by myelin protein zero (P0) promoter (Yamauchi et al., 1999) were crossed with two transgenic lines that have lacZ or GFP gene (Kawamoto et al., 2000). Neural crest derived–cells (NCDCs) were specifically labeled by reporter gene expression in each double transgenic mouse. To examine the distribution of NCDCs, these double transgenic lines were crossed with Pax6Sey/+mice (Hill et al., 1991).
In Pax6Sey/+ mice, NCDCs abnormally migrated into the developing eye in a cell non–autonomous manner at early embryonic stages. Furthermore, various eye defects in the Pax6Sey/+ mice were accompanied by abnormal distribution of NCDCs from early developmental stages to the adult. Pax6Sey/+ eyes showed a wide range of anomalies both in the anterior segment and the vitreous, in association with the aberrant distribution of NCDCs.
These results indicate that normal distribution and integration of NCDCs in the ocular tissues depend on a proper dosage of Pax6, and that the ocular anomalies of Pax6Sey/+ are caused by combinational cell autonomous and non–autonomous defects due to Pax6 haploinsufficiency.
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