Abstract
ABSTRACTOrganogenesis requires precise interactions between a developing tissue and its environment. In vertebrates, the developing eye is surrounded by a complex extracellular matrix as well as multiple mesenchymal cell populations. Disruptions to either the matrix or periocular mesenchyme can cause defects in early eye development, yet in many cases the underlying mechanism is unknown. Here, using multidimensional imaging and computational analyses in zebrafish, we establish that cell movements in the developing optic cup require neural crest. Ultrastructural analysis reveals that basement membrane formation around the developing eye is also dependent on neural crest, but only specifically around the retinal pigment epithelium. Neural crest cells produce the extracellular matrix protein nidogen: impairing nidogen function disrupts eye development, and, strikingly, expression of nidogen in the absence of neural crest partially restores optic cup morphogenesis. These results demonstrate that eye formation is regulated in part by extrinsic control of extracellular matrix assembly.This article has an associated ‘The people behind the papers’ interview.
Highlights
Vertebrate optic cup morphogenesis requires precise coordination of cell and tissue movements, which generate the shape and organization crucial for eye function (Hilfer, 1983; Schmitt and Dowling, 1994; Schook, 1980; Walls, 1942)
We find that optic cup formation is impaired in mutants exhibiting a severe loss of neural crest, and 4-dimensional timelapse imaging demonstrates neural crest cells migrate around the eye during optic cup morphogenesis
Given that neural crest is in close proximity to the developing retinal pigment epithelium (RPE) throughout eye morphogenesis and no other basement membranes (BM) around the eye are disrupted in tfap2a;foxd3 mutants, these results suggest that neural crest contributes to BM development or stability around the RPE
Summary
Vertebrate optic cup morphogenesis requires precise coordination of cell and tissue movements, which generate the shape and organization crucial for eye function (Hilfer, 1983; Schmitt and Dowling, 1994; Schook, 1980; Walls, 1942). Lineage tracing and live imaging, especially in recent work in zebrafish, has enabled detailed analyses of cell movements during eye development, including identification of extended evagination and rim movement (Heermann et al, 2015; Kwan et al, 2012; Li et al, 2000; Picker et al, 2009; Sidhaye and Norden, 2017). Rim movement occurs during invagination: a subset of cells from the medial layer of the optic vesicle moves around the rim of the vesicle and contributes to the lateral layer, the prospective neural retina. The molecular mechanisms governing rim movement and invagination are only partly understood; much work remains to be done to identify extrinsic cues regulating these dramatic cell movements and changes in morphology. Two potential sources of such extrinsic cues are the extracellular matrix (ECM) and nearby cell populations
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