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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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Telencephalic and diencephalic gene expression in the fgf16 morphants.The expression of emx1 (A, B), tbr1 (C, D), dlx2 (E, F), pax6a (G, H), and shh (I, J) in wild-type embryos (A, C, E, G, I) and fgf16 morphants (B, D, F, H, J) at 24 hpf. Arrows in panels A and C indicate the subpallial telencephalon, which was negative for emx1 or tbr1. Dots indicate the boundary between the telencephalon and ventral diencephalon. Lateral views with anterior to the left and dorsal to the top.
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pone-0110836-g004: Telencephalic and diencephalic gene expression in the fgf16 morphants.The expression of emx1 (A, B), tbr1 (C, D), dlx2 (E, F), pax6a (G, H), and shh (I, J) in wild-type embryos (A, C, E, G, I) and fgf16 morphants (B, D, F, H, J) at 24 hpf. Arrows in panels A and C indicate the subpallial telencephalon, which was negative for emx1 or tbr1. Dots indicate the boundary between the telencephalon and ventral diencephalon. Lateral views with anterior to the left and dorsal to the top.

Mentions: fgf3, fgf8, and fgf19 have been implicated in patterning events in the zebrafish forebrain [7], [8], [18]–[20]. Therefore, we investigated whether Fgf16 was also involved in the regionalization of the forebrain. The expression of telencephalon marker genes was analyzed in fgf16 morphants at 24 hpf. The expression of emx1, which is normally detected in the pallial domain of the telencephalon, was observed in the entire region of the telencephalon in fgf16 morphants (n = 28/32) (Fig. 4A, B). Furthermore, the expression of tbr1, which normally occurs in the pallial telencephalon, was also detected in the entire telencephalon in fgf16 morphants (n = 15/16) (Fig. 4C, D). In contrast to the expression of emx1 and tbr1, that of dlx2, which is normally detected in the ventral region of the telencephalon, was reduced in fgf16 morphants (n = 27/31) (Fig. 4E, F). On the other hand, the expression of pax6a, which is normally detected in the telencephalon, was unaffected in fgf16 morphants (n = 21/21) (Fig. 4G, H). The ectopic expression of otx2 was detected in the ventral region of the telencephalon in fgf16 morphants at 24 hpf (n = 13/13) (Fig. 5C, D). In contrast, all control embryos showed normal expression patterns for these genes (data not shown). These results indicated that fgf16 was required for the development of the subpallial telencephalon.


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)

Telencephalic and diencephalic gene expression in the fgf16 morphants.The expression of emx1 (A, B), tbr1 (C, D), dlx2 (E, F), pax6a (G, H), and shh (I, J) in wild-type embryos (A, C, E, G, I) and fgf16 morphants (B, D, F, H, J) at 24 hpf. Arrows in panels A and C indicate the subpallial telencephalon, which was negative for emx1 or tbr1. Dots indicate the boundary between the telencephalon and ventral diencephalon. 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-g004: Telencephalic and diencephalic gene expression in the fgf16 morphants.The expression of emx1 (A, B), tbr1 (C, D), dlx2 (E, F), pax6a (G, H), and shh (I, J) in wild-type embryos (A, C, E, G, I) and fgf16 morphants (B, D, F, H, J) at 24 hpf. Arrows in panels A and C indicate the subpallial telencephalon, which was negative for emx1 or tbr1. Dots indicate the boundary between the telencephalon and ventral diencephalon. Lateral views with anterior to the left and dorsal to the top.
Mentions: fgf3, fgf8, and fgf19 have been implicated in patterning events in the zebrafish forebrain [7], [8], [18]–[20]. Therefore, we investigated whether Fgf16 was also involved in the regionalization of the forebrain. The expression of telencephalon marker genes was analyzed in fgf16 morphants at 24 hpf. The expression of emx1, which is normally detected in the pallial domain of the telencephalon, was observed in the entire region of the telencephalon in fgf16 morphants (n = 28/32) (Fig. 4A, B). Furthermore, the expression of tbr1, which normally occurs in the pallial telencephalon, was also detected in the entire telencephalon in fgf16 morphants (n = 15/16) (Fig. 4C, D). In contrast to the expression of emx1 and tbr1, that of dlx2, which is normally detected in the ventral region of the telencephalon, was reduced in fgf16 morphants (n = 27/31) (Fig. 4E, F). On the other hand, the expression of pax6a, which is normally detected in the telencephalon, was unaffected in fgf16 morphants (n = 21/21) (Fig. 4G, H). The ectopic expression of otx2 was detected in the ventral region of the telencephalon in fgf16 morphants at 24 hpf (n = 13/13) (Fig. 5C, D). In contrast, all control embryos showed normal expression patterns for these genes (data not shown). These results indicated that fgf16 was required for the development of the subpallial telencephalon.

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