Biology subjects

Le Bail, R.

Publications and source records attributed to Le Bail, R..

4 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2024

Ccp1 depletion disrupts network integration of hippocampal parvalbumin interneurons

Post-translational modifications (PTMs) of microtubules (MTs) endow them with specific properties that are essential for key cellular functions, such as axonal transport. Polyglutamylation, a PTM that accumulates in long-lived MTs, has been linked to neurodegeneration in the cerebellum when in excess. While hyperglutamylation of MTs leads to neurodegeneration and disrupts the function of specific neuronal subtypes like Purkinje cells, cortical neurons, and hippocampal excitatory neurons, little is known about its impact on inhibitory interneurons and their functional integration into local networks. In this study, we generated a conditional knockout mouse model to deplete cytosolic carboxypeptidase 1 (Ccp1) in GABAergic neurons, a key MT deglutamylase expressed by hippocampal interneurons. Our findings reveal that the loss of Ccp1 has a profound effect on hippocampal parvalbumin (PV)-expressing interneurons, impairing their axonal transport and reducing their perisomatic inhibition of pyramidal cells (PCs) in the CA2 region of the hippocampus. Research TopicsMolecular Neuroscience, Cell Biology HighlightsO_LIDifferent subtypes of hippocampal interneurons express unique sets of (de)glutamylases and show varying levels of protein posttranslational glutamylation. C_LIO_LIParvalbumin interneurons become hyperglutamylated when Ccp1 activity is lost. C_LIO_LIThe loss of Ccp1 disrupts axonal transport in interneurons and is associated with decreased perisomatic inhibition of hippocampal pyramidal cells in the CA2 region. C_LI

neuroscience↗

bioRxiv2020

ATP-Citrate lyase fuels axonal transport across species

Microtubule (MT)-based transport is an evolutionary conserved processed finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, which is catalyzed by the α-tubulin N-acetyltransferase 1, Atat1, promotes the recruitment and processivity of molecular motors along MT tracks. However, the mechanisms that controls Atat1 activity remains poorly understood. Here, we show that a pool of vesicular ATP-citrate lyase Acly acts as a rate limiting enzyme to modulate Atat1 activity by controlling availability of Acetyl-Coenzyme-A (Acetyl-CoA). In addition, we showed that Acly expression is reduced upon loss of Elongator activity, further connecting Elongator to Atat1 in the pathway regulating α-tubulin acetylation and MT-dependent transport in projection neurons, across species. Remarkably, comparable defects occur in fibroblasts from Familial Dysautonomia (FD) patients bearing an autosomal recessive mutation in the gene coding for the Elongator subunit ELP1. Our data may thus shine new light on the pathophysiological mechanisms underlying FD.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗

bioRxiv2019

ATAT1-enriched vesicles promote microtubule acetylation via axonal transport

Microtubules are polymerized dimers of - and {beta}-tubulin that underlie a broad range of cellular activities. Acetylation of -tubulin by the acetyl-transferase ATAT1 modulates microtubule dynamics and functions in neurons. However, it remains unclear how and why this enzyme acetylates microtubules over long distances in axons. Here, we show that loss of ATAT1 impairs axonal transport in neurons and cell free motility assays confirm a requirement of tubulin acetylation for proper bidirectional vesicular transport. Moreover, we demonstrate that the main cellular pool of ATAT1 is transported at the cytosolic side of neuronal vesicles that are moving along axons. Altogether, our data suggest that axonal transport of ATAT1-enriched vesicles is the predominant driver of -tubulin acetylation in axons.

neuroscience↗