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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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Morphology of the brain in fgf16 morphants.Dorsal views of wild-type (A), fgf16 MO-injected (B), and fgf16 MO- and fgf16 RNA-injected (C) embryos at 24 hpf. Arrows indicate the MHB constriction.
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pone-0110836-g001: Morphology of the brain in fgf16 morphants.Dorsal views of wild-type (A), fgf16 MO-injected (B), and fgf16 MO- and fgf16 RNA-injected (C) embryos at 24 hpf. Arrows indicate the MHB constriction.

Mentions: We previously showed that zebrafish fgf16 was expressed in the pectoral fin bud and also that the knockdown of fgf16 function resulted in the absence of fin bud outgrowth at 5 days post-fertilization (dpf) [29]. In addition, the brain structures of fgf16 morphants exhibited abnormalities at 5 dpf [29]. fgf16 morphants were morphologically distinguishable from the wild type at 24 hours post-fertilization (hpf). fgf16 morphants showed morphological abnormalities in the forebrain at 24 hpf (Fig. 1B). Furthermore, fgf16 morphants were morphologically defective in the formation of midbrain-hindbrain boundary (MHB) constriction and exhibited a failure to evaginate laterally in the midbrain at 24 hpf (Fig. 1B). The gross morphological phenotypes obtained by an injection of either fgf16 MO1 or fgf16 MO2 were similar to each other (MO1, n = 78/89 and MO2, n = 79/112). On the other hand, control MO-injected embryos developed normally during embryogenesis [9]. Furthermore, the phenotype was confirmed by RNA rescue experiments. The co-injection of fgf16 RNA with fgf16 MO1 rescued the brain defects caused by fgf16 MO1 (n = 10/13) (Fig. 1C). These results suggested that fgf16 may be required for normal development in the forebrain and midbrain, and the formation of MHB constriction during neurogenesis.


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)

Morphology of the brain in fgf16 morphants.Dorsal views of wild-type (A), fgf16 MO-injected (B), and fgf16 MO- and fgf16 RNA-injected (C) embryos at 24 hpf. Arrows indicate the MHB constriction.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0110836-g001: Morphology of the brain in fgf16 morphants.Dorsal views of wild-type (A), fgf16 MO-injected (B), and fgf16 MO- and fgf16 RNA-injected (C) embryos at 24 hpf. Arrows indicate the MHB constriction.
Mentions: We previously showed that zebrafish fgf16 was expressed in the pectoral fin bud and also that the knockdown of fgf16 function resulted in the absence of fin bud outgrowth at 5 days post-fertilization (dpf) [29]. In addition, the brain structures of fgf16 morphants exhibited abnormalities at 5 dpf [29]. fgf16 morphants were morphologically distinguishable from the wild type at 24 hours post-fertilization (hpf). fgf16 morphants showed morphological abnormalities in the forebrain at 24 hpf (Fig. 1B). Furthermore, fgf16 morphants were morphologically defective in the formation of midbrain-hindbrain boundary (MHB) constriction and exhibited a failure to evaginate laterally in the midbrain at 24 hpf (Fig. 1B). The gross morphological phenotypes obtained by an injection of either fgf16 MO1 or fgf16 MO2 were similar to each other (MO1, n = 78/89 and MO2, n = 79/112). On the other hand, control MO-injected embryos developed normally during embryogenesis [9]. Furthermore, the phenotype was confirmed by RNA rescue experiments. The co-injection of fgf16 RNA with fgf16 MO1 rescued the brain defects caused by fgf16 MO1 (n = 10/13) (Fig. 1C). These results suggested that fgf16 may be required for normal development in the forebrain and midbrain, and the formation of MHB constriction during neurogenesis.

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