Fezf2 promotes neuronal differentiation through localised activation of Wnt/β-catenin signalling during forebrain development

Abstract

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.

Hypothalamic radial glia function as self-renewing neural progenitors in the absence of Wnt/ß-catenin signaling

“…We found that a specific subset of lef1-dependent neurons located near the hypothalamic ventricle arise from the radial glial lineage . Combined with other studies in the retina (Agathocleous et al, 2009), cerebral cortex (Munji et al, 2011;Zhang et al, 2014), hippocampus (Seib et al, 2013) and midbrain (Castelo-Branco et al, 2003), our data suggest that the most widely conserved role for Wnt/β-catenin signaling in the CNS might be to regulate the differentiation of specific subsets of committed neural progenitors.…”

Assessing Primary Neurogenesis in <em>Xenopus</em> Embryos Using Immunostaining

“…In such cases, either Morpholinos (MOs) or DNA construct(s) carrying promoter-driven gene(s) are injected into one of the two blastomeres at two-cell stage 23 . Alternatively, they can be injected into the brain ventricle followed by electroporation, which will result in knockdown or over-expression of desired gene(s) 27 .…”

“…Therefore, to track proliferation, differentiation, and movement of neuronal cells in live animals, it would be desired to establish one or more transgenic lines that harbor fluorescent proteins driven by cell typespecific promoter to allow live observation of such cell populations in early Xenopus embryos. The establishment of a X. laevis line with neurospecific β-tubulin promoter driving tauGFP and its applications have provided a nice example 23,34 . With the full promoter sequences of both sox3 and myt1 characterized in vertebrates [35][36][37] , it is should be relatively easy to establish additional transgenic lines in Xenopus which should contribute extensively to both the Xenopus community and a more general field of primary neurogenesis research.…”

“…Further investigations into these mechanisms require a reliable method to easily visualize and distinguish different populations of neuronal cells. The above-mentioned neural markers, including, Sox3, Myt1, and Ntub, can provide a means for identifying these different cell populations, thus providing the necessary foundations for revealing the underlying mechanisms of neuronal differentiation [21][22][23] .…”

Phospholipase A2-activating protein is associated with a novel form of leukoencephalopathy

“…Specifically, disruption of cell-cell adhesion function of Armadillo results in construction defects of the axonal scaffold (Loureiro and Peifer, 1998). Interestingly, a recent study suggested that PLA 2 a regulates the Wnt/b-catenin pathway (Han et al, 2008), which is implicated in neurogenesis, CNS morphogenesis, hirsutism, sweat gland morphology, short tendons, and kyphosis (Toribio et al, 2010;Haara et al, 2011;Joksimovic and Awatramani, 2014;Zhang et al, 2014). In this pathway, b-catenins transduce Wnt signals during embryonic development.…”