Manipulation of the nuclear envelope-associated protein SLAP during mammalian brain development affects cortical lamination and exploratory behavior.

Here, we report the first characterization of the effects resulting from the manipulation of Soluble-Lamin Associated Protein (SLAP) expression during mammalian brain development. We found that SLAP localizes to the nuclear envelope and when overexpressed causes changes in nuclear morphology and lengthening of mitosis. SLAP overexpression in apical progenitors of the developing mouse brain altered asymmetric cell division, neurogenic commitment and neuronal migration ultimately resulting in unbalance in the proportion of upper, relative to deeper, neuronal layers. Several of these effects were also recapitulated upon Cas9-mediated knockdown. Ultimately, SLAP overexpression during development resulted in a reduction in subcortical projections of young mice and, notably, reduced their exploratory behavior. Our study shows the potential relevance of the previously uncharacterized nuclear envelope protein SLAP in neurodevelopmental disorders.

Amphiphilic Block Copolymers PEG-b-PMTCs: Synthesis, Self-Assembly, Degradation Properties and Biocompatibility.

As a hydrophilic cyclic ketene acetal (CKA), 2-methylene-1,3,6-trioxocane (MTC) has recently attracted a lot of attention owing to its ability to promote a quicker (bio)degradation as compared to other heavily studied CKAs. Here, we prepared amphiphilic block copolymers based on poly-MTC with varying chain lengths by radical ring opening polymerization. Self-assemblies of these amphiphiles were performed in PBS buffer to generate nanoparticles with sizes from 40 to 105 nm, which were verified by dynamic light scattering, electron microscopy, and static light scattering (Zimm plots). Subsequently, fluorescence spectroscopy was applied to study the enzymatic degradation of Nile red-loaded nanoparticles. By performing a point-by-point comparison of fluorescence intensity decline patterns between nanoparticles, we demonstrated that lipase from Pseudomonas cepacia was very efficient in degrading the nanoparticles. Hydrolysis degradations under basic conditions were also carried out, and a complete degradation was achieved after 4 h. Additionally, cytotoxicity assays were carried out on HEK293 cells, and the results affirmed cell viabilities over 90% when incubated with up to 1 mg/mL nanoparticles for 24 h. These biodegradable and biocompatible nanoparticles hence hold great potential for future applications such as drug release.