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Gallego-Lopez, I.

Publications and source records attributed to Gallego-Lopez, I..

3 recordsLinked to original sources

Evolution Shapes Cortical Interneuron Migration

The cerebral cortex comprises excitatory neurons and inhibitory interneurons originating from distinct forebrain regions. During migration, cortical interneurons (cINs) interact dynamically with neighbouring cells and their microenvironment, contributing to cortical architecture. However, how evolutionary changes in cIN migration shape species-specific cortical development remains unclear. Comparative analyses in mouse, ferret, and human models revealed a conserved migratory sequence but distinct behaviours: human cINs migrate slower, display increased leading-process branching, and exhibit more frequent homotypic repulsive interactions than their mouse and ferret counterparts. These features promote dispersed cortical invasion of cINs in humans and ferrets, contrasting with the stream-like migration observed in mice. Mechanistically, elevated expression of the cytosolic carboxypeptidase CCP1 in human cINs reduces microtubule glutamylation and doublecortin recruitment, thereby facilitating leading-process branching. These findings identify a CCP1-dependent mechanism regulating cIN dispersion and suggest that evolutionary changes in cIN migration contribute to divergent patterns of cortical morphogenesis across mammals.

neuroscience↗

Species-specific Rates of Fatty Acid MetabolismSet the Scale of Temporal Patterning of Corticogenesisthrough Protein Acetylation Dynamics

Developmental processes display temporal differences across species, leading to divergence in organ size and composition. In the cerebral cortex, neurons of diverse identities are generated sequentially through a temporal patterning mechanism conserved throughout mammals. This corticogenesis process is considerably prolonged in the human species, leading to increased brain size and complexity, but the underlying molecular mechanisms remain largely unknown. Here we found that human cortical progenitors displayed lower levels of fatty acid oxidation than their mouse counterparts, in line with their protracted pattern. Treatments that enhance mitochondrial fatty acid oxidation (FAO) accelerated the development of human cortical organoids, including faster progression of neural progenitor cell fate and precocious generation of late-born neurons and glia. FAO accelerated temporal patterning through increased Acetyl-CoA-dependent protein acetylation, including on specific histone transcriptional marks. Thus, species-specific metabolic rates regulate the turnover of post-translation modifications to set the scale of temporal gene regulatory networks of corticogenesis.

neuroscience↗

Size-Dependent Expression of the Fission Yeast Cdc13 Cyclin is Conferred by Translational Regulation

The major fission yeast cyclin, Cdc13, has been shown to increase in concentration in correlation with cell size, and has been proposed to thereby regulate cell size at division. However, the mechanism of its cell-size regulation has been unknown. Here, we show that Cdc13 is regulated post-transcriptionally. Its transcript is not expressed in a size-dependent manner, rather a size-dependent concentration of protein is expressed from a size-independent concentration of mRNA. Moreover, we show that the expression of Cdc13 is, in fact, size dependent, as opposed to simply size-correlated due to time-dependent expression. We identify a 20-amino-acid motif, which includes the APC D-box degron, as necessary and sufficient for size-dependent expression, which allowed us to construct a size-independent allele of cdc13. Using this allele, we show that size-dependent expression of Cdc13 is not required for size control in fission yeast cells.

cell biology↗