Herrgen L , Akerman CJ .

BB/E015476/1 Biotechnology and Biological Sciences Research Council , BB_BB/E015476/1 Biotechnology and Biological Sciences Research Council , ERC_243273 European Research Council, ERC_617670 European Research Council, 243273 European Research Council, 617670 European Research Council

             neuron differentiation
             neuron development

	Figure 1 The optic tectum of Xenopus laevis develops from a neuroepithelium where the great majority of progenitors divides apically. (A) Head of a stage 48 Xenopus laevis. FB, forebrain. MB, midbrain. HB, hindbrain. OT, optic tectum. Scale bar represents 200 μm. (B) The posterior‐lateral region of the optic tectum comprises a neuroepithelium. NE, neuroepithelium. P, pia. V, ventricle. Scale bar represents 10 μm. (C) Mitotic cells (dashed circle) can be identified after staining for F‐actin (green) and cell nuclei (magenta). Scale bar represents 10 μm. (D) Summary diagram showing the localization of mitotic cells. n = 10 animals. Scale bar represents 10 μm. [Color figure can be viewed at wileyonlinelibrary.com.]
	Figure 2 Single‐cell in vivo time‐lapse imaging of neural progenitors reveals four different types of progenitor cell behavior. Each row of the figure comprises three panels showing an animal's left optic tectum on consecutive days. The first image in each row was taken 1‐3 h after single‐cell electroporation. (A‐C) A radial progenitor electroporated with fluorescent dextran (A) undergoes a proliferative symmetric division and generates two radial progenitor cells (B), and further divisions produce four cells (C). Scale bars in main panel and inset represent 10 μm and 5 μm, respectively. (D‐F) A radial progenitor cell (D) undergoes a neurogenic asymmetric division, which generates another radial progenitor and a non‐radial neuron (E). The newborn neuron subsequently migrates away from the ventricular surface (F). (G‐I) A radial progenitor (G) undergoes a neurogenic symmetric division and generates two non‐radial neurons. The newborn neurons then migrate away from the ventricular surface (H) and develop neurites (I). (J‐K) A radial progenitor cell (J) undergoes direct neuronal differentiation by retracting its radial processes (K) and developing neurites (L). (M‐O) A non‐radial cell (M) does not divide over several days but instead moves away from the ventricular surface (N) and starts to develop neurites (O).
	Figure 3 Proliferative and neurogenic progenitors are spatially separated along the anterior‐posterior axis of the developing optic tectum. (A) Progenitors in the posterior part of the tectum undergo proliferative divisions, whereas those located more anteriorly generate neurons. The positions of cell bodies indicate the apical‐basal extent of the neuroepithelium. PD, proliferative division. ND, neurogenic division. DD, direct neuronal differentiation. n = 42 animals. Scale bar represents 10 μm. (B) Quantification of the prevalence of different types of cell behavior within 20 μm bins along the ventricular wall. The vertical dashed line indicates the boundary between regions of proliferative and neurogenic behavior. P, proliferative. N, neurogenic. [Color figure can be viewed at wileyonlinelibrary.com.]
	Figure 4 Tectal progenitors and their progeny are repositioned relative to the heel during development. (A‐C) The positions of four radial progenitors (A) and their progeny relative to the heel change as they divide (B) and mature (C), while their positions relative to each other are maintained. Scale bar represents 10 μm. (D) Measurement of the positions of the individual progenitors and their progeny in (A‐C) relative to the heel over three days.
	Figure 5 The expression pattern of HuC/D within the neuroepithelium parallels the spatial distribution of neurogenic progenitors. (A) The optic tectum stained for HuC/D (green) and cell nuclei (magenta). The most posteriorly located HuC/D+ cells (arrowheads) are found near the pial surface of the neuroepithelium. The vast majority of HuC/D+ cells resides in the neuronal layer, which overlies the neuroepithelium in the anterior tectum. Scale bar represents 10 μm. (B) HuC/D immunoreactivity from the image shown in (A). (C) Quantification of the distribution of neurogenic progenitors as assessed by in vivo time‐lapse imaging, and quantification of the distribution of HuC/D+ cells, along the anterior‐posterior axis of the neuroepithelium. n = 42 and 41 animals for in vivo time‐lapse imaging and HuC/D staining, respectively. (D) The optic tectum stained for HuC/D after electroporation. The panel is a composite of two images from two different animals. Scale bar represents 10 μm. (E) The radial cell does not express HuC/D (filled arrowheads), whereas all four non‐radial cells express HuC/D (open arrowheads). SCE, single‐cell electroporation. Scale bar represents 10 μm. [Color figure can be viewed at wileyonlinelibrary.com.]
	Figure 6 Neural progenitor divisions are predominantly planar but oblique and vertical divisions are increased in the neurogenic region of the optic tectum. (A,C) The optic tectum stained for F‐actin (green) and cell nuclei (magenta), revealing planar (A) and vertical (C) progenitor divisions. Scale bar represents 5 μm. (B,D) Higher magnification images of the dividing cells in (A) and (C). Scale bar represents 2 μm. (E) Distribution of cleavage angle orientation along the anterior‐posterior axis of the optic tectum. n = 76 animals. (F) The majority of divisions are planar, although there is an increase in the proportion of oblique and vertical divisions in the neurogenic region. *, p < 0.05 in Fisher's exact test. [Color figure can be viewed at wileyonlinelibrary.com.]
	Figure 7 The length of the cell cycle, S phase and G1 phase differ between proliferative and neurogenic regions of the optic tectum. (A‐D) The optic tectum stained for BrdU (green) and cell nuclei (magenta) after 2 hours (A), 6 hours (B), 14 hours (C) and 30 hours (D) of incubation with BrdU. P, proliferative region. N, neurogenic region. Scale bar represents 10 μm. (E‐H) BrdU immunoreactivity from the images shown in (A‐D). (I) Quantification of the fraction of BrdU+ cells over time in the proliferative and neurogenic regions. n = 22 animals. (J) Length of cell cycle (left) and length of S phase (right) in proliferative and neurogenic regions. (K) The optic tectum stained for phospho‐histone H3 (green) and cell nuclei (magenta). Phospho‐histone H3+ cells (arrowheads) exhibited clear somatic labeling and reside near the ventricular wall. In contrast, staining in the neuronal region is not associated with cell somata. n = 6 animals. Scale bar represents 10 μm. (L) Phospho‐histone H3 immunoreactivity from the image shown in (K). (M) Combined length of G2 phase and M phase (left) and length of G1 phase (right) in proliferative and neurogenic regions. All population data are displayed as mean ± sem. **p < 0.01 in unpaired t‐test with Welch's correction. [Color figure can be viewed at wileyonlinelibrary.com.]

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