Wnt and Shh signals regulate neural stem cell proliferation and differentiation in the optic tectum of adult zebrafish

Abstract

Adult neurogenesis occurs more commonly in teleosts, represented by zebrafish, than in mammals. Zebrafish is therefore considered a suitable model to study adult neurogenesis, for which the regulatory molecular mechanisms remain little known. Our previous study revealed that neuroepithelial‐like neural stem cells (NSCs) are located at the edge of the dorsomedial region. We also showed that Notch signaling inhibits NSC proliferation in this region. In the present study, we reported the expression of Wnt and Shh signaling components in this region of the optic tectum. Moreover, inhibitors of Wnt and Shh signaling suppressed NSC proliferation, suggesting that these pathways promote NSC proliferation. Shh is particularly required for maintaining Sox2‐positive NSCs. Our experimental data also indicate the involvement of these signaling pathways in neural differentiation from NSCs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1206–1220, 2017

Involvement of sonic hedgehog and notch signaling in regenerative neurogenesis in adult zebrafish optic tectum after stab injury

“…We previously showed that Shh signal‐related genes are expressed in the adult optic tectum and that Shh signaling regulates NE proliferation and differentiation (Shitasako et al, ). In our previous study, it was suggested that Shh signaling up‐regulates NE proliferation and down‐regulates NE differentiation under physiological conditions.…”

“…We previously showed that some genes related to Shh signaling, including shha , smo , ptch1 , and ptch2 , are expressed in the adult optic tectum (Shitasako et al, ). Shh ligand binds to transmembrane receptor Patched (Ptch) and Ptch activation leads to the inhibition of Smoothened (Smo) (Lum & Beach, ).…”

“…In the present study, we investigated the role of Shh and Notch signaling in proliferation and differentiation of RG in both physiological and regenerative conditions. We previously showed that some genes related to Shh signaling, including shha, smo, ptch1, and ptch2, are expressed in the adult optic tectum (Shitasako et al, 2017). Shh ligand binds to transmembrane receptor Patched (Ptch) and Ptch activation leads to the inhibition of Smoothened (Smo) (Lum & Beach, 2004).…”

“…The inhibition of Smo results in the transcriptional response mediated by Gli transcription factor (Kasper, Regl, Frischauf, & Aberger, 2006). The Shh receptors, smo, ptch1, and ptch2 are expressed in RG of the adult zebrafish optic tectum (Shitasako et al, 2017). In the present study, we analyzed the activity of canonical Shh signaling after stab injury using Shh signaling reporter line in which Green fluorescent protein (GFP) expression is induced in response to canonical Shh activation.…”

Wnt signaling regulates proliferation and differentiation of radial glia in regenerative processes after stab injury in the optic tectum of adult zebrafish

“…The function of NE in the regenerative condition and RG in both, physiological and regenerative conditions, are not well known. In the previous studies, we analyzed the function of Wnt signaling on adult neurogenesis in the optic tectum of zebrafish (Shitasako et al, ), and Wnt‐related genes were expressed in the central nervous system of the zebrafish embryo (Clements, Ong, & Traver, ; Duncan, Panahi, Piotrowski, & Dorsky, ; Hashimoto et al, ; Untergasser, Martowicz, Hermann, Töchterle, & Meyer, ). Moreover, other studies also showed that Wnt signaling regulates self‐renewal and differentiation of neural stem cells in the physiological and regenerative conditions in the retina, hypothalamus, and spinal cord (McPherson et al, ; Ramachandran, Zhao, & Goldman, ; Strand et al, ).…”