Fgf signaling in the zebrafish adult brain: Association of Fgf activity with ventricular zones but not cell proliferation

Abstract

The zebrafish adult brain contains numerous neural progenitors and is a good model to approach the general mechanisms of adult neural stem cell maintenance and neurogenesis. Here we use this model to test for a correlation between Fgf signaling and cell proliferation in adult progenitor zones. We report expression of Fgf signals (fgf3,4,8a,8b,17b), receptors (fgfr1-4), and targets (erm, pea3, dusp6, spry1,2,4, and P-ERK) and document that genes of the embryonic fgf8 synexpression group acquire strikingly divergent patterns in the adult brain. We further document the specific expression of fgf3, fgfr1-3, dusp6, and P-ERK in ventricular zones, which contain neural progenitors. In these locations, however, a comparison at the single-cell level of fgfr/P-ERK expression with bromo-deoxy-uridine (BrdU) incorporation and the proliferation marker MCM5 indicates that Fgf signaling is not specifically associated with proliferating progenitors. Rather, it correlates with the ventricular radial glia state, some of which only are progenitors. Together these results stress the importance of Fgf signaling in the adult brain and establish the basis to study its function in zebrafish, in particular in relation to adult neurogenesis.

Stem Cells in the Adult Zebrafish Cerebellum: Initiation and Maintenance of a Novel Stem Cell Niche

“…Although we found expression of fgfr2 in the stem cell niche, we did not detect markers for high levels of Fgf signaling activity in the proliferating cells. This is in agreement with a recent study showing that Fgf activity is not associated with stem cell activity in the adult zebrafish brain (Topp et al, 2008). However, our results clearly show that stem cell activity is reduced when Fgf signaling is blocked, suggesting that Fgf signaling is important for stem cell regulation in the adult cerebellum.…”

“…However, our results clearly show that stem cell activity is reduced when Fgf signaling is blocked, suggesting that Fgf signaling is important for stem cell regulation in the adult cerebellum. Interestingly, Fgfs ( fgf3, fgf8a, and fgf8b) are expressed in the adult zebrafish cerebellum (Topp et al, 2008), although only in close proximity to the ventricle and not directly at the stem cell niche. It is therefore an attractive possibility that Fgfs might propagate through the ventricle in the cerebellum.…”

Modulation of Fgfr1a Signaling in Zebrafish Reveals a Genetic Basis for the Aggression–Boldness Syndrome

“…4a,b) and pERK (Fig. 4c,d), readouts of Fgf signaling in the adult brain (Topp et al, 2008). We observed a reduction of both dusp6 and pERK in the periventricular nucleus of the inferior lobe of the hypothalamus (PVN; Fig.…”

“…Zebrafish have multiple Fgf receptors that are coexpressed in the adult brain. For example, fgfr1a, fgfr2, and fgfr3 are all expressed in the PVN, central nucleus, and diffuse nucleus of the hypothalamus (Topp et al, 2008). Both fgfr2 and fgfr3 are expressed normally throughout the brain of homozygous spd mutants.…”

“…In situ hybridization was performed according to Norton et al (2008) and antibody staining according to Topp et al (2008). The following in situ hybridization probes were used in this study: dusp6; fgfr1a; mao; npvf; pomcb; slc6a4a; and slc6a4b.…”