The Role of FOXP1 in the Differentiation of Mouse Ocular Tissue

• Main Authors: Do-Wen Chen, 陳鐸文
• Other Authors: An-Guor Wang
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/90912464467719956230

碩士 === 國立陽明大學 === 神經科學研究所 === 101 === Abstract FOXP1 is a transcription factor related to the regulation of proliferation. In post two decades, the role of FOXP1 on tumor growth inhibition, heart development and monocyte differentiation has been well studied. Nevertheless, the mechanism of how FOXP1 regulates cell differentiation is still unclear. In 2004, anti-G2s autoantibody was found to be present in patients with thyroid-associated ophthalmopathy, and this autoantibody is presumed to be the main cause for this autoimmune disorder. The auto-antigen G2s was later found to be identical to the C-terminus of FOXP1. Since FOXP1 is a transcription factor, it is presumed to be expressed within the nucleus. If it is the autoantigen for the thyroid-associated ophthalmopathy, we are interested to find out the expression pattern of FOXP1 in the extraocular muscle. In earlier study, our laboratory has found that FOXP1 protein was expressed in the cytoplasm and on the membrane of adult human extraocular muscles. In vitro study using C2C12 cell line showed that FOXP1 is located in the nucleus while seeding and will translocate into cytoplasm of fused myotube after induction of differentiation. To explore the in-vivo expression of FOXP1 in the developing extraocular muscle, we used embryonic mice to examine its expression by immunostaining in this study. We found the FOXP1 was located exclusively in nucleus at E12.5 and E13.5, and some signal of FOXP1 would start to form the myotube shape from E14.5 to E17.5. In P1 and adult mice, most of FOXP1 signal was expressed in the cytoplasm of the myotube. We were also interested to know whether the FOXP1 plays a role in the developmental process on other parts of the eye. So we observed the expression of FOXP1 in the retina and lens during embryonic development. In retina development, we found the FOXP1 was located in nucleus of retinal neurons from E12.5 to E14.5. However, some FOXP1 signals decreased in nucleus and formed into a long shape in the outer retina of E15.5, E17.5, P1, and P5. In adult mice, FOXP1 protein was expressed in the cytoplasm of photoreceptor cells, surrounding the nucleus. In lens development, we found FOXP1 was expressed within nucleus at E12.5 to E15.5. After E17.5, FOXP1 signals still can be observed in cytoplasm of primary fiber cells, but no nucleus FOXP1 detectable. We used P19 cell as neural differentiation model to further check the expression of FOXP1. By immunocytochemistry, we found the FOXP1 is expressed mainly in the nucleus of undifferentiated P19 cells. Under differentiated condition, it will be expressed not only in the nucleus but also on the outgrowing neurites, which is labeled with MAP2. With cell fractionation study, we found there was not only a nucleus-cytoplasmic translocation, but also a change of FOXP1 protein isoforms once it was induced to differentiate. These results indicate that FOXP1 protein plays an important role in the development of ocular structures and different isoforms may have various functions in the differentiation process.