The hemispheric, bi-layered optic cup forms from an oval optic vesicle during early vertebrate eye development through major morphological transformations. The overall basal surface, facing the developing lens, is increasing, while, at the same time, the space basally occupied by individual cells is decreasing. This cannot be explained by the classical view of eye development. Using zebrafish (Danio rerio) as a model, we show that the lens-averted epithelium functions as a reservoir that contributes to the growing neuroretina through epithelial flow around the distal rims of the optic cup. We propose that this flow couples morphogenesis and retinal determination. Our 4D data indicate that future stem cells flow from their origin in the lens-averted domain of the optic vesicle to their destination in the ciliary marginal zone. BMP-mediated inhibition of the flow results in ectopic neuroretina in the RPE domain. Ultimately the ventral fissure fails to close resulting in coloboma.DOI:
http://dx.doi.org/10.7554/eLife.05216.001
Highlights d Btd/Eve-dependent lateral MyoII shortens cells to initiate CF d Single-cell row Btd/Eve positional code accounts for only 80% of CF-initiating cells d Mis-specification arises due to MyoII noise, and yet the cells align among themselves d Mechanical coupling via planar polarized MyoII aligns cells to ensure CF linearity
Optic cup morphogenesis is an intricate process. Especially, the formation of the optic fissure is not well understood. Persisting optic fissures, termed coloboma, are frequent causes for congenital blindness. Even though the defective fusion of the fissure margins is the most acknowledged reason for coloboma, highly variable morphologies of coloboma phenotypes argue for a diverse set of underlying pathomechanisms. Here, we investigate optic fissure morphogenesis in zebrafish to identify potential morphogenetic defects resulting in coloboma. We show that the formation of the optic fissure depends on tissue flow movements, integrated into the bilateral distal epithelial flow forming the optic cup. On the temporal side, the distal flow translates into a ventral perpendicular flow, shaping the temporal fissure margin. On the nasal side, however, the distal flow is complemented by tissue derived from the optic stalk, shaping the nasal fissure margin. Notably, a distinct population of TGFβ-signalling positive cells is translocated from the optic stalk into both fissure margins. Furthermore, we show that induced BMP signalling as well as Wnt-signalling inhibition result in morphogenetic defects of the optic fissure. Our data also indicate that morphogenesis is crucial for a proper positioning of pre-specified dorsal–ventral optic cup domains.
Muthinja, M. J. et al. (2017) Microstructured blood vessel surrogates reveal structural tropism of motile malaria parasites. Advanced Healthcare Materials, 6(6), 1601178. (doi:10.1002/adhm.201601178) There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it. This is the peer-reviewed version of the following article: Muthinja, M. J. et al. (2017) Investigating the association of sporozoites to pillars in arrays displaying pillars of different diameters revealed that the crescent-shaped parasites prefer to associate with and migrate around pillars with a similar curvature. This suggests that after transmission by a mosquito malaria parasites might use a structural tropism to recognize blood capillaries in the dermis in order to gain access to the blood stream.4
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