期刊
DEVELOPMENT
卷 143, 期 21, 页码 3895-3906出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.134601
关键词
Morphogenesis; Organoid culture; Pattern formation; Retinal development
资金
- RIKEN Junior Research Associate Program
- Japan Society for the Promotion of Science KAKENHI [24680037]
- Ministry of Education, Culture, Sports, Science, and Technology
- Network Program for Realization of Regenerative Medicine from the Japan Science and Technology Agency
- Grants-in-Aid for Scientific Research [16H06485, 16H04799, 24680037] Funding Source: KAKEN
We previously demonstrated that mouse embryonic stem cell (mESC)-derived retinal epithelium self-forms an optic cup-like structure. In the developing retina, the dorsal and ventral sides differ in terms of local gene expression and morphological features. This aspect has not yet been shown in vitro. Here, we demonstrate that mESC-derived retinal tissue spontaneously acquires polarity reminiscent of the dorsal-ventral (D-V) patterning of the embryonic retina. Tbx5 and Vax2 were expressed in a mutually exclusive manner, as seen in vivo. Three-dimensional morphometric analysis showed that the in vitro-formed optic cup often contains cleft structures resembling the embryonic optic fissure. To elucidate the mechanisms underlying the spontaneous D-V polarization of mESC-derived retina, we examined the effects of patterning factors, and found that endogenous BMP signaling plays a predominant role in the dorsal specification. Further analysis revealed that canonical Wnt signaling, which was spontaneously activated at the proximal region, acts upstream of BMP signaling for dorsal specification. These observations suggest that D-V polarity could be established within the self-formed retinal neuroepithelium by intrinsic mechanisms involving the spatiotemporal regulation of canonical Wnt and BMP signals.
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