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Development 2014 Dec 01;14124:4794-805. doi: 10.1242/dev.115691.
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Fezf2 promotes neuronal differentiation through localised activation of Wnt/β-catenin signalling during forebrain development.

Zhang S , Li J , Lea R , Vleminckx K , Amaya E .

Brain regionalisation, neuronal subtype diversification and circuit connectivity are crucial events in the establishment of higher cognitive functions. Here we report the requirement for the transcriptional repressor Fezf2 for proper differentiation of neural progenitor cells during the development of the Xenopus forebrain. Depletion of Fezf2 induces apoptosis in postmitotic neural progenitors, with concomitant reduction in forebrain size and neuronal differentiation. Mechanistically, we found that Fezf2 stimulates neuronal differentiation by promoting Wnt/β-catenin signalling in the developing forebrain. In addition, we show that Fezf2 promotes activation of Wnt/β-catenin signalling by repressing the expression of two negative regulators of Wnt signalling, namely lhx2 and lhx9. Our findings suggest that Fezf2 plays an essential role in controlling when and where neuronal differentiation occurs within the developing forebrain and that it does so by promoting local Wnt/β-catenin signalling via a double-repressor model.

PubMed ID: 25468942
PMC ID: PMC4299278
Article link: Development
Grant support: [+]

Species referenced: Xenopus
Genes referenced: arx barhl2 bmp4 chrd.1 ctnnb1 fezf2 foxh1.2 gsc irx3 lhx2 lhx9 myt1 neurog1 nodal3.1 otx2 pax6 ptk2b rax rpl8 sia1 smad1 smad2 sox3 tle1 tle2 tle4 tle5 tuba4b tubb2b ventx1 ventx1.2 wnt1 wnt3a wnt8a wnt8b
Antibodies: FLAG Ab1 Myt1 Ab1 Sox3 Ab2 Tuba4b Ab4
Morpholinos: fezf2 MO2 lhx2 MO1 lhx9 MO1

Article Images: [+] show captions
References [+] :
Akkers, ChIP-chip designs to interrogate the genome of Xenopus embryos for transcription factor binding and epigenetic regulation. 2010, Pubmed, Xenbase