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Fgf16 is required for specification of GABAergic neurons and oligodendrocytes in the zebrafish forebrain.

Miyake A, Chitose T, Kamei E, Murakami A, Nakayama Y, Konishi M, Itoh N - PLoS ONE (2014)

Bottom Line: The knockdown of fgf16 decreased cell proliferation in the forebrain and midbrain. fgf16 was also essential for development of the ventral telencephalon and diencephalon, whereas fgf16 was not required for dorsoventral patterning in the midbrain. fgf16 was additionally required for the specification and differentiation of γ-aminobutyric acid (GABA)ergic interneurons and oligodendrocytes, but not for those of glutamatergic neurons in the forebrain.The fgf16 morphant phenotype was similar to that of the fgf19 morphant and embryos blocked Hh signaling.The results of the present study indicate that Fgf16 signaling, which is regulated by the downstream pathways of Hh-Fgf19 in the forebrain, is involved in forebrain development.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo, Kyoto, Japan.

ABSTRACT
Fibroblast growth factor (Fgf) signaling plays crucial roles in various developmental processes including those in the brain. We examined the role of Fgf16 in the formation of the zebrafish brain. The knockdown of fgf16 decreased cell proliferation in the forebrain and midbrain. fgf16 was also essential for development of the ventral telencephalon and diencephalon, whereas fgf16 was not required for dorsoventral patterning in the midbrain. fgf16 was additionally required for the specification and differentiation of γ-aminobutyric acid (GABA)ergic interneurons and oligodendrocytes, but not for those of glutamatergic neurons in the forebrain. Cross talk between Fgf and Hedgehog (Hh) signaling was critical for the specification of GABAergic interneurons and oligodendrocytes. The expression of fgf16 in the forebrain was down-regulated by the inhibition of Hh and Fgf19 signaling, but not by that of Fgf3/Fgf8 signaling. The fgf16 morphant phenotype was similar to that of the fgf19 morphant and embryos blocked Hh signaling. The results of the present study indicate that Fgf16 signaling, which is regulated by the downstream pathways of Hh-Fgf19 in the forebrain, is involved in forebrain development.

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Interactions between fgf16 and Hh signaling in the forebrain and midbrain.The expression of fgf16 at 16 (A, B) and 24 (C, D) hpf in wild-type embryos treated with 0.95% ethanol (A, C) or cyclopamine (B, D). Arrows in panels A and C indicate fgf16 expression in the telencephalon. The arrowhead in panel C indicates fgf16 expression in the midbrain. Lateral views with anterior to the left and dorsal to the top.
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pone-0110836-g008: Interactions between fgf16 and Hh signaling in the forebrain and midbrain.The expression of fgf16 at 16 (A, B) and 24 (C, D) hpf in wild-type embryos treated with 0.95% ethanol (A, C) or cyclopamine (B, D). Arrows in panels A and C indicate fgf16 expression in the telencephalon. The arrowhead in panel C indicates fgf16 expression in the midbrain. Lateral views with anterior to the left and dorsal to the top.

Mentions: Hh signaling in the ventral forebrain functions in dorsoventral (D/V) forebrain patterning and promotes the GABAergic neuronal/oligodendrocyte lineage restriction of forebrain stem cells [44], [76], [77]. The inhibition of fgf16 led to abnormalities in the regionalization and generation of specific cell types such as GABAergic interneurons and oligodendrocytes in the forebrain. Hh signaling is critical for regulating the expression of fgf3, fgf8, and fgf19 in the forebrain and that of fgf19 and fgf22 in the midbrain [8], [9]. Therefore, we examined whether the expression of Fgf16 was responsive to Hh signaling. Since the alkaloid cyclopamine completely blocked Hh signaling at the level of Smoothened, which transduces Hh signals, in zebrafish [8], [78], we examined the expression of Fgf16 in embryos treated with cyclopamine. In embryos treated with cyclopamine, fgf16 expression was lost in the forebrain at 16 and 25 hpf (n = 16/16 and n = 10/10, respectively) (Fig. 8A–D). Furthermore, fgf16 expression in the midbrain was lost in embryos treated with cyclopamine (n = 10/10) (Fig. 8C, D). All control embryos showed normal expression patterns for these genes (Fig. 8A, C). These results indicated that the expression of Fgf16 in the forebrain and midbrain was dependent on Hh signaling.


Fgf16 is required for specification of GABAergic neurons and oligodendrocytes in the zebrafish forebrain.

Miyake A, Chitose T, Kamei E, Murakami A, Nakayama Y, Konishi M, Itoh N - PLoS ONE (2014)

Interactions between fgf16 and Hh signaling in the forebrain and midbrain.The expression of fgf16 at 16 (A, B) and 24 (C, D) hpf in wild-type embryos treated with 0.95% ethanol (A, C) or cyclopamine (B, D). Arrows in panels A and C indicate fgf16 expression in the telencephalon. The arrowhead in panel C indicates fgf16 expression in the midbrain. Lateral views with anterior to the left and dorsal to the top.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214708&req=5

pone-0110836-g008: Interactions between fgf16 and Hh signaling in the forebrain and midbrain.The expression of fgf16 at 16 (A, B) and 24 (C, D) hpf in wild-type embryos treated with 0.95% ethanol (A, C) or cyclopamine (B, D). Arrows in panels A and C indicate fgf16 expression in the telencephalon. The arrowhead in panel C indicates fgf16 expression in the midbrain. Lateral views with anterior to the left and dorsal to the top.
Mentions: Hh signaling in the ventral forebrain functions in dorsoventral (D/V) forebrain patterning and promotes the GABAergic neuronal/oligodendrocyte lineage restriction of forebrain stem cells [44], [76], [77]. The inhibition of fgf16 led to abnormalities in the regionalization and generation of specific cell types such as GABAergic interneurons and oligodendrocytes in the forebrain. Hh signaling is critical for regulating the expression of fgf3, fgf8, and fgf19 in the forebrain and that of fgf19 and fgf22 in the midbrain [8], [9]. Therefore, we examined whether the expression of Fgf16 was responsive to Hh signaling. Since the alkaloid cyclopamine completely blocked Hh signaling at the level of Smoothened, which transduces Hh signals, in zebrafish [8], [78], we examined the expression of Fgf16 in embryos treated with cyclopamine. In embryos treated with cyclopamine, fgf16 expression was lost in the forebrain at 16 and 25 hpf (n = 16/16 and n = 10/10, respectively) (Fig. 8A–D). Furthermore, fgf16 expression in the midbrain was lost in embryos treated with cyclopamine (n = 10/10) (Fig. 8C, D). All control embryos showed normal expression patterns for these genes (Fig. 8A, C). These results indicated that the expression of Fgf16 in the forebrain and midbrain was dependent on Hh signaling.

Bottom Line: The knockdown of fgf16 decreased cell proliferation in the forebrain and midbrain. fgf16 was also essential for development of the ventral telencephalon and diencephalon, whereas fgf16 was not required for dorsoventral patterning in the midbrain. fgf16 was additionally required for the specification and differentiation of γ-aminobutyric acid (GABA)ergic interneurons and oligodendrocytes, but not for those of glutamatergic neurons in the forebrain.The fgf16 morphant phenotype was similar to that of the fgf19 morphant and embryos blocked Hh signaling.The results of the present study indicate that Fgf16 signaling, which is regulated by the downstream pathways of Hh-Fgf19 in the forebrain, is involved in forebrain development.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo, Kyoto, Japan.

ABSTRACT
Fibroblast growth factor (Fgf) signaling plays crucial roles in various developmental processes including those in the brain. We examined the role of Fgf16 in the formation of the zebrafish brain. The knockdown of fgf16 decreased cell proliferation in the forebrain and midbrain. fgf16 was also essential for development of the ventral telencephalon and diencephalon, whereas fgf16 was not required for dorsoventral patterning in the midbrain. fgf16 was additionally required for the specification and differentiation of γ-aminobutyric acid (GABA)ergic interneurons and oligodendrocytes, but not for those of glutamatergic neurons in the forebrain. Cross talk between Fgf and Hedgehog (Hh) signaling was critical for the specification of GABAergic interneurons and oligodendrocytes. The expression of fgf16 in the forebrain was down-regulated by the inhibition of Hh and Fgf19 signaling, but not by that of Fgf3/Fgf8 signaling. The fgf16 morphant phenotype was similar to that of the fgf19 morphant and embryos blocked Hh signaling. The results of the present study indicate that Fgf16 signaling, which is regulated by the downstream pathways of Hh-Fgf19 in the forebrain, is involved in forebrain development.

Show MeSH
Related in: MedlinePlus