探討新型自主感光視神神經細胞之發育及其功能

自從視黑質被發現後,自主感光視神神經細胞(ipRGCs)被發現參參與了了許多非成像視覺功能,例例如生理理週期及瞳孔光反射。在視神神經細胞的發育中,brn3b (POU4F2) 是個常見見的轉錄錄因子。儘管大部份的 ipRGCs 表現 brn3b,卻有少部分的 ipRGCs 不不表現 brn3b,這些 ipRGCs 主要支配了了下視丘中的視交叉上核(SCN),而 SCN 的功能為哺乳類類動物的生理理時鐘中樞。在視網膜發育的過程中,不不同時間點分化出來來的細胞往往形成不不同的細胞種類類。為了了找出這些 brn3b 陰性 ipRGCs 的分化時程,我們利利用缺乏 brn3b 陽性 ipRGCs 的基因轉殖小鼠,以及野生型小鼠,以 5-乙炔基-2’-去氧尿尿苷(EdU)和視黑質免疫染色來來標定在特定時間點進行行細胞分裂裂的 ipRGCs。我們的資料料顯示 brn3b 陰性 ipRGCs 與全體的 ipRGCs,從前驅細胞分化出來來的時間範圍並無顯著差異異。更更進一步分析這些細胞的分佈範圍,發現 brn3b 陰性 ipRGCs 與全體 ipRGCs 在發育的空間進程上有些微的差異異。另一方面,針對 brn3b 陰性 ipRGCs 與視交叉上核所主導的生理理時鐘,藉由雙眼及單眼的生理理時鐘相位移實驗的結果,提供日後相關研究的參參考。

關鍵字

Brn3b 陰性 M1 型自主感光視神神經細胞；視交叉上核；視網膜發育；生理理時鐘

並列摘要

Since the melanopsin was discovered, the novel photoreceptor, melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), have been shown to participate in many non-image forming functions such as circadian rhythms and pupillary light reflex. While most ipRGCs express brn3b (POU4F2), the general transcription factor for retinal ganglion cells development, a portion of ipRGCs do not express brn3b and dominantly innervate suprachiasmatic nucleus (SCN), which is the central clock for circadian rhythm in mammals. In retinal development, different time points of cell differentiation strongly imply different cell types. To identify differentiation time point of brn3b negative ipRGCs, we used 5-ethynyl-2’-deoxyuridine (EdU) and melanopsin immunostaining to label mitotic ipRGCs at specific embryonic stage in wild type mice and transgenic mice without brn3b-expressing ipRGCs. Our data show that brn3b negative ipRGCs and the whole population of ipRGCs derive from retinal progenitor cells in the same period. Further analysis in spatial iii distribution discovered slight difference at progression of development. In addition, to assess the circadian rhythms that brn3b negative M1 ipRGCs and SCN involve, circadian phase shift experiments of one-eye light pulse and two-eye light pulse were done, and the results provide some insights for researches in the future.

並列關鍵字

brn3b negative M1 intrinsically photosensitive retinal ganglion cells ； suprachiasmatic nucleus ； retinal development ； cell birthdate ； circadian rhythm

參考文獻

Abrahamson, E. E., & Moore, R. Y. (2001). Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res, 916(1-2), 172-191.

Badea, T. C., Cahill, H., Ecker, J., Hattar, S., & Nathans, J. (2009). Distinct roles of transcription factors brn3a and brn3b in controlling the development, morphology, and function of retinal ganglion cells. Neuron, 61(6), 852-864. doi: 10.1016/j.neuron.2009.01.020

Baver, S. B., Pickard, G. E., Sollars, P. J., & Pickard, G. E. (2008). Two types of melanopsin retinal ganglion cell differentially innervate the hypothalamic suprachiasmatic nucleus and the olivary pretectal nucleus. Eur J Neurosci, 27(7), 1763-1770. doi: 10.1111/j.1460-9568.2008.06149.x

Brzezinski, J. A. t., Prasov, L., & Glaser, T. (2012). Math5 defines the ganglion cell competence state in a subpopulation of retinal progenitor cells exiting the cell cycle. Dev Biol, 365(2), 395-413. doi: 10.1016/j.ydbio.2012.03.006

Cepko, C. (2014). Intrinsically different retinal progenitor cells produce specific types of progeny. Nat Rev Neurosci, 15(9), 615-627. doi: 10.1038/nrn3767

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探討新型自主感光視神神經細胞之發育及其功能

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