[Molecular biological approaches to eye development].
Many genes are expressed coordinately and proteins coded by these genes interact with one another in development of the eye. Candidates for such factors are growth factors, hormones, and their receptors, transcriptional factors such as homeodomain-containing proteins. The following experiments were done in order to understand their roles in eye development. I. Analysis of Pax-6 gene in a rat strain with small eye phenotype. A mutant rat strain "rSey (rat small eye)" showed absence of both the nasal placode and the lens placode in homozygotes, which resulted in nasal malformation and lack of the eyes. This phenotype was similar to that of a mouse mutant "Sey (small eye)" with mutations of the Pax-6 gene, which motivated me to analyze the Pax-6 gene in the mutant rat. An exon of the Pax-6 genomic DNA in the homozygote had a novel dinucleotide (GT) due to one base (G) insertion, which served as an abnormal 5' donor splice site and generated an internal deletion of the messenger RNA. The homozygote also showed impaired migration of neural crest cells originating from the anterior midbrain, indicating that the Pax-6 gene would be conducting migration of the neural crest cells. II. Localization of transcripts by in situ hybridization. 1. Retinoic acid receptor. Retinoic acids are teratogenic and exposure to them causes facial malformation including eye anomalies. Three types (alpha, beta, gamma) are known as receptors for all-trans retinoic acids. Transcripts for all the types were found in neural crest and its derivatives around and inside of the optic cup in mouse embryos. The finding is consistent with the fact that neural crest cells are involved in malformation caused by retinoic acids. 2. Fibroblast growth factor. Fibroblast growth factors exert effects on differentiation, proliferation, and survival of various kinds of cells in the eye. Three types (types 1, 2, and 3) of fibroblast growth factor receptors have been discovered in chick. The type 1 receptor was expressed mainly in the neuroepithelial layers of the optic cup, and the type 2 receptor was expressed in mesenchymal cells of neural crest origin around the optic cup of chick embryos. In contrast, transcripts for the type 3 receptor were detected at a high level in the lens vesicle. Different types of the receptor expressed in structures of different origins indicate that fibroblast growth factors would be involved in signaling among these different structures in eye development. 3. Activin receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
Matsuo
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Department of Ophthalmology, Okayama University Medical School.
D029404:Activin Receptors; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005123:Eye / Q000196:embryology*; D005124:Eye Abnormalities / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics
D005136:Eye Proteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D017978:Receptors, Growth Factor; D029404:Activin Receptors