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Dissecting the role of Wnt signaling and its interactions with FGF signaling during midbrain neurogenesis

Research output: Contribution to journalArticlepeer-review

Carlene Jane Dyer, Eric Blanc, Robin Stanley Johnson, Robert Knight

Original languageEnglish
Article numbere1057313
JournalNeurogenesis
Volume2
Issue number1
Early online date21 Sep 2015
DOIs
Accepted/In press27 May 2015
E-pub ahead of print21 Sep 2015

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Abstract

Interactions between FGF and Wnt/ bcat signaling control development of the midbrain. The nature of this interaction and how these regulate patterning, growth and differentiation is less clear, as it has not been possible to temporally dissect the effects of one pathway relative to the other. We have employed pharmacological and genetic tools to probe the temporal and spatial roles of FGF and Wnt in controlling the specification of early midbrain neurons. We identify a β-catenin (bcat) independent role for GSK-3 in modulating FGF activity and hence neuronal patterning. This function is complicated by an overlap with bcat-dependent regulation of FGF signaling, through the regulation of sprouty4. Additionally we reveal how attenuation of Axin protein function can promote fluctuating levels of bcat activity that are dependent on FGF activity. This highlights the complex nature of the interactions between FGF and Wnt/ bcat and reveals that they act at multiple levels to control each others activity in the midbrain.

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