Specification of dorsal telencephalic character by sequential Wnt and FGF signaling

Gunhaga, Lena; Marklund, Matthew; Sjödal, My; Hsieh, Ju-Ton; Jessell, Thomas M.; Edlund, Thomas

doi:10.1038/nn1068

Cited by 178 publications

(154 citation statements)

References 46 publications

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“…Specifically, FGFs have been shown to play an important role in development of the neocortex. FGF2 (34) and FGF8 (35) recently have been shown to interact with Wnt in development of the cortex in mouse and chick embryos, respectively. In the adult brain, FGF2 promotes neuronal survival and axonal branching (36), and its mRNA expression is increased by various stressors in multiple brain regions (37).…”

Section: Discussionmentioning

confidence: 99%

“…Before probe hybridization, tissue was fixed in 4% paraformaldehyde at room temperature, rinsed with aqueous buffers, and dehydrated with graded alcohols. Riboprobes were synthesized with incorporation of 35 S-UTP and 35 S-CTP and hybridized to tissue overnight at 55°C. Sections were washed with increasing stringency, dehydrated with graded alcohols, airdried, and exposed to film.…”

Section: In Situ Hybridization (Ish)mentioning

confidence: 99%

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Dysregulation of the fibroblast growth factor system in major depression

Evans

Choudary

Neal

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

382

272

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In this report we describe findings that imply dysregulation of several fibroblast growth factor (FGF) system transcripts in frontal cortical regions of brains from human subjects with major depressive disorder (MDD). This altered gene expression was discovered by microarray analysis of frontal cortical tissue from MDD, bipolar, and nonpsychiatric control subjects and was verified by quantitative real-time PCR analysis and, importantly, in a separate cohort of MDD subjects. Furthermore, we show, through a separate analysis of specific serotonin reuptake inhibitor (SSRI)-treated and non-SSRI-treated MDD subjects that the observed changes in expression of FGF transcripts are not secondary to drug treatment. Rather, changes in specific FGF transcripts are attenuated by SSRIs and may thus be partially responsible for the mechanism of action of these drugs. We also make available the gene-expression profile of all of the other growth factors and growth factor receptors detected in these postmortem samples.

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Section: Discussionmentioning

confidence: 99%

Section: In Situ Hybridization (Ish)mentioning

confidence: 99%

Dysregulation of the fibroblast growth factor system in major depression

Evans

Choudary

Neal

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

382

272

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“…Juxtaposed sources of Shh, Fgf8, and BMP/Wnt proteins regulate one another to pattern the telencephalon (Crossley et al, 2001;Ohkubo et al, 2002;Shimogori et al, 2004) but are not the only patterning cues. Given that dorsal epidermis induces roofplate in the spinal cord (Liem et al, 1995) and dorsal gene expression in the chick telencephalon (Gunhaga et al, 2003), dorsal telencephalic midline inductive signals seem likely to derive from adjacent mesenchyme and epidermis.…”

Section: Discussionmentioning

confidence: 99%

Patterning the Dorsal Telencephalon: A Role for Sonic Hedgehog?

Rash¹,

Grove²

2007

J. Neurosci.

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Division of the telencephalic vesicle into hemispheres and specification of the cerebral cortex are key stages in forebrain development. We investigate the interplay in these processes of Sonic hedgehog (Shh), fibroblast growth factors (Fgfs), and the transcription factor Gli3, which in its repressor form (Gli3R) antagonizes Shh signaling and downregulates expression of several Fgf genes.Contrary to previous reports, Shh is not required for dorsal hemisphere separation. Mice lacking Shh develop a dorsal telencephalic midline, a cortical hem, and two cortical hemispheres. The hemispheres do not divide rostrally, probably because of reduced local Fgf gene expression, resulting from the loss of Shh inhibition of Gli3R. Removing one functional copy of Gli3 substantially rescues Fgf expression and rostral telencephalic morphology.In mice lacking Gli3 function, cortical development is arrested, and ventral gene expression invades the dorsal telencephalon. These defects are potentially explained by disinhibition of Shh activity. However, when both copies of Shh are removed from Gli3-null mice, dorsal telencephalic defects persist. One such defect is a large dorsal expansion of the expression of Fgf genes. Fgf15 expression, for example, expands from a discrete ventral domain throughout the dorsal telencephalon. We propose that Fgf signaling, known to ventralize the telencephalon in a Shh-independent manner, suppresses cortical fate in the absence of Gli3. Our findings point away from Shh involvement in dorsal telencephalic patterning and encourage additional exploration of Fgf signaling and Gli3 repression in corticogenesis.

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“…The wnt family interacts with a set of receptors encoded by the fzd genes [49,86], with signals transduced by the dvl group and negatively modulated by the dkk genes [37]. Importantly for our work, the fgf and wnt families are coexpressed in adjacent locations within the developing brain and deletion of genes from either group produces parallel defects in forebrain development [9,38,66,69,70,100]. As in our earlier work [79], we utilized microarrays to examine the key members of each gene family, comparing similarities and differences in the effects of chlorpyrifos and diazinon: if the involvement of neurotrophic mechanisms is unrelated to the inhibition of cholinesterase, then there are likely to be significant disparities between the two agents.…”

Section: Introductionmentioning

confidence: 85%

Targeting of neurotrophic factors, their receptors, and signaling pathways in the developmental neurotoxicity of organophosphates in vivo and in vitro

Slotkin¹,

Seidler²,

Fumagalli³

2008

Brain Research Bulletin

127

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Neurotrophic factors control neural cell differentiation and assembly of neural circuits. We previously showed that organophosphate pesticides differentially regulate members of the fibroblast growth factor (fgf) gene family. We administered chlorpyrifos and diazinon to neonatal rats on postnatal days 1-4 at doses devoid of systemic toxicity or growth impairment, and spanning the threshold for barely-detectable cholinesterase inhibition. We evaluated the impact on gene families for different classes of neurotrophic factors. Using microarrays, we examined the regional expression of mRNAs encoding the neurotrophins (ntfs), brain-derived neurotrophic factor (bdnf), nerve growth factor (ngf), the wnt and fzd gene families and the corresponding receptors. Chlorpyrifos and diazinon both had widespread effects on the fgf, ntf, wnt and fzd families but much less on the bdnf and ngf groups. However, the two organophosphates showed disparate effects on a number of key neurotrophic factors. To determine if the actions were mediated directly on differentiating neurons, we tested chlorpyrifos in PC12 cells, an in vitro model of neural cell development. Effects in PC12 cells mirrored many of those for members of the fgf, ntf and wnt families, as well as the receptors for the ntfs, especially during early differentiation, the stage known to be most susceptible to disruption by organophosphates. Our results suggest that actions on neurotrophic factors provide a mechanism for the developmental neurotoxicity of low doses of organophosphates, and, since effects on expression of the affected genes differed with test agent, may help explain regional disparities in effects and critical periods of vulnerability.

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Specification of dorsal telencephalic character by sequential Wnt and FGF signaling

Cited by 178 publications

References 46 publications

Dysregulation of the fibroblast growth factor system in major depression

Dysregulation of the fibroblast growth factor system in major depression

Patterning the Dorsal Telencephalon: A Role for Sonic Hedgehog?

Targeting of neurotrophic factors, their receptors, and signaling pathways in the developmental neurotoxicity of organophosphates in vivo and in vitro

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