Biology subjects

Lopez-Atalaya, J. P.

Publications and source records attributed to Lopez-Atalaya, J. P..

2 recordsLinked to original sources

bioRxiv2019

Zic2 abrogates an alternative Wnt signaling pathway to convert axon attraction into repulsion

Wnt signaling is involved in axon pathfinding during brain wiring but it is unknown how Wnt ligands promote attraction or repulsion. In addition, the participation of the canonical ({beta}catenin-dependent transcription) versus non-canonical ({beta}catenin-independent) Wnt pathways in this process remains controversial. Here we show that Wnt5a is expressed at the optic chiasm midline and promotes axon crossing by triggering an alternative Wnt pathway that depends on polarized accumulation of {beta}catenin at the axon terminal but does not activate the canonical pathway. Remarkably, this alternative pathway is silenced by the transcription factor Zic2 in the small subset of ipsilaterally projecting neurons. Zic2 directly regulates genes related to Wnt and Eph signaling that lead to global accumulation of {beta}catenin but triggers its asymmetric phosphorylation to facilitate the steering of the growth cone. This alternative Wnt pathway found in contralateral axons and its Zic2-mediated abrogation in ipsilateral neurons is likely operating in many other contexts requiring a two-way response to Wnt ligands.

developmental biology↗

bioRxiv2019

MIR3607 regulates cerebral cortex development via activation of Wnt/βCat signaling

The evolutionary expansion of the mammalian cerebral cortex is recapitulated during embryonic development in large mammals, but the underlying genetic mechanisms remain mostly unknown. Previous transcriptomic analyses of the developing ferret cortex identify candidate genes related to the expansion of germinal layers and cortex size. Here we focused on MIR3607, a microRNA differentially expressed between germinal layers of the large human and ferret cortex, not expressed in the small mouse cortex. Expression of MIR3607 in mouse embryos at E14.5 leads to increased progenitor cell proliferation. This is reflected in transcriptomic changes, which also reveal increased Wnt/{beta}Catenin signaling. Expression of MIR3607 at E12.5, when progenitor cells expand, causes amplification and severe delamination of apical progenitors, leading to rosette formation. This is rescued by co-expressing Adenomatous Polyposis Coli, inhibitor of canonical Wnt signaling. A similar phenotype is produced in human cerebral organoids. Our findings demonstrate that MIR3607 expands and delaminates apical progenitor cells via activating Wnt/{beta}Catenin, and suggest that a secondary loss of expression in mouse may underlie their reduction in cortex size during recent evolution.

developmental biology↗