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.
Highlights
The forebrain becomes regionally subdivided into the telencephalon and diencephalon during early embryonic brain development in vertebrates
Our results demonstrated that fgf16 was critical for cell proliferation in the forebrain and midbrain. fgf16 was critical for development of the ventral region of the telencephalon and diencephalon, and was implicated in the specification of c–aminobutyric acid (GABA)ergic interneurons and oligodendrocytes in the telencephalon and diencephalon
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)
Summary
The forebrain becomes regionally subdivided into the telencephalon and diencephalon during early embryonic brain development in vertebrates. The regional specification, growth, and differentiation of telencephalic and diencephalic subdivisions are controlled by interactions between secreted signaling molecules. The dorsal region of the telencephalon coordinates growth and patterning via Bone morphogenetic proteins (Bmps) and Wnts [2]. Hedgehog (Hh) signaling is known to be critical for ventral patterning in the forebrain and midbrain [3,4,5]. Fibroblast growth factor (Fgf) signaling has been implicated in dorsoventral patterning and the regulation of cell proliferation and differentiation in various regions during brain development [1,6,7,8,9]
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