(A–A’) Schematic representation of zebrafish retinal development: (A) Neuronal birth and migration (48 hours post fertilization [hpf]). Neuroepithelial progenitors (gray) divide at the apical side and give birth to five major neuron types:photoreceptor (PR), HC, bipolar cell (BC), amacrine cell (AC), retinal ganglion cell (RGC). (A’) The layered organization of the mature zebrafish retina (92 hpf). Retinal neurons and a single type of retina glial cell, MGs, are arranged in three nuclear layers from apical to basal: outer nuclear layer (ONL), inner nuclear layer (INL), ganglion cell layer (GCL). These layers are separated by two plexiform layers: outer plexiform layer (OPL) and inner plexiform layer (IPL). The basement membrane (BM) separates the GCL from the vitreous body. (B) Scheme of bidirectional and bimodal migration of an HC progenitor and its committed precursors. Division of neuroepithelial progenitor (gray) generates HC progenitors (HCprs) (light green). HCprs display a bipolar morphology and are attached to the apical surface during the first phase of migration. Upon apical detachment, HCprs show multipolar morphology. En route to their destination, multipolar HCprs undergo a terminal mitosis to generate two HCs (green), which migrate toward the HC layer. Arrowhead: detachment of HCpr from the apical surface and onset of multipolar migration. Gray line: a representative HC migration trajectory (see also stills and trajectory in Figure 1—figure supplement 1A-B). (C) Time-lapse of HC tangential migration before BC lamination (50 hpf). Tg(vsx-1:GFP) labels BCs (magenta) and Tg(ptf1a:DsRed) marks HCs (green). White dot: tracked HC. Time in h:min. Scale bar: 10 μm. (D) Basal-to-apical migration trajectories of HCs before and after emergence of mature radially oriented BCs and MGs. HCs use both radial (apical-basal) and tangential (lateral) routes to move within the INL. See Figure 1—source data 1. (E) Maximum projections of retinae at different developmental stages: 38, 55, 65, 70, and 90 hpf. Tg(ptf1a:dsRed) labels HCs and ACs (green) and Tg(gfap:GFP) labels MGs (magenta). 38 hpf: birth and initiation of HC basal migration. GFAP+ cells are progenitors. 55 hpf: initiation of HC apical migration. 65 hpf: peak of HC apical migration. Higher magnification inset of the outlined region shows an HC at its final destination (arrow), and a migrating HC en route to the apical side (arrowhead). 70 hpf: emergence of the HC layer and MG maturation. arrows: show HCs within the HC layer. 90 hpf: mature and fully laminated retina. Scale bars: 50 μm, inset 65 hpf: 10 μm. See also Figure 1—figure supplement 1.
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