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Molecular genetic regulation of eye field development (EyeDevelopment)
Start date: 01 Jun 2009, End date: 31 May 2013 PROJECT  FINISHED 

Anophthalmia and microphthalmia, birth defects that are important causes of childhood blindness, often arise as a result of abnormal development of eye progenitors in the eye field during early embryogenesis. The molecular genetic mechanisms that underlie eye progenitor development in the eye field are not well understood. This proposal aims to identify cellular, molecular and genetic mechanisms of eye progenitor development during the eye field stage using zebrafish as a model organism. We will focus on regulation of eye field development by the transcription factor Six3, whose loss of function has been shown to cause anophthalmia or microphthalmia in humans and several genetic model organisms including zebrafish. We will use a combination of in vivo studies with genetic and molecular approaches toward two specific objectives: first, we will identify cellular mechanisms underlying loss of eye progenitors during eye field stage in Six3-deficient zebrafish embryos, which exhibit anophthalmia or microphthalmia. This will be achieved by following eye progenitors in live Six3-deficient embryos and determining their fates. Subsequent analyses will address the molecular mechanisms that lead to these fates. The second specific objective will identify protein-coding genes and miRNAs that are important for eye field development, with focus on downstream targets of Six3. This will be achieved using a transgenic approach to isolate eye field cells from wild-type and Six3-deficient embryos and identify protein-coding genes and miRNAs that are specifically expressed in the eye field and whose expression is affected by the loss of Six3 function. Together, these studies will lead to better understanding of the genetic network that underlies early eye development. Such knowledge is necessary for improving the ability to provide genetic counseling and may also help in prevention of severe eye malformation.
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