Biology subjects

Lopez-Bendito, G.

Publications and source records attributed to Lopez-Bendito, G..

6 recordsLinked to original sources

bioRxiv2025

Combinatorial Cell-Adhesion and Activity Codes Instruct Cortical Modality Identity

The emergence of functional sensory modalities requires precise cortical arealization and appropriate thalamocortical targeting. Although early morphogen gradients set broad cortical territories, the mechanisms that specify sensory identity and guide modality-specific thalamocortical targeting remain unknown. Here, we identify an embryonic set of activity-independent cortical "protogenes", prominently enriched for cell-adhesion molecules, that are differentially expressed between primary somatosensory (S1) and visual (V1) cortices prior to thalamic innervation. These adhesion programs are selectively localized to layer 4, the main thalamo-recipient layer, and strikingly mirror the adhesion profiles of their corresponding thalamic nuclei, suggesting partner recognition. Disrupting thalamic activity alters modality-specific spontaneous cortical dynamics and the postnatal expression of another set of modality-specific genes, indicating a modulatory role for thalamic activity in cortical identity. These findings support a two-step model in which cortical identity is primed by adhesion codes driving modality-specific thalamocortical targeting, and later refined by patterned thalamic activity to establish functional cortical modalities.

neuroscience↗

bioRxiv2025

Early lineage divergence segregates sensory and non-sensory thalamic circuits

The thalamus integrates sensory, motor, and associative functions via distinct nuclei, yet the developmental principles driving their specification remains unclear. Here, we generate a spatiotemporal single-cell multiomic and spatial transcriptomic atlas of the embryonic mouse thalamus, combined with barcoding-based lineage tracing. We identify two major glutamatergic lineages--sensory and motor/associative--each governed by different gene regulatory programs and temporal dynamics. These lineages arise from spatially and molecularly isolated progenitors, revealing an early segregation of functional identities. Within the sensory lineage, we resolve two discrete trajectories leading to first-order visual and somatosensory neurons, both emerging from a shared higher-order default state. Using in silico predictions and in vivo perturbations, we identify Sp9 as a key regulator of visual thalamic fate. Together, our findings define the molecular architecture and developmental trajectories that underpin thalamic modality specification, providing a framework to understand how functional circuits emerge in the mammalian brain.

neuroscience↗

bioRxiv2024

Purkinje cell intrinsic activity shapes cerebellar development and function

The emergence of functional cerebellar circuits is heavily influenced by activity-dependent processes. However, the role of intrinsic activity in Purkinje neurons, independent of external input, in driving cerebellar development remains less understood. Here, we demonstrate that before synaptic networks mature, Purkinje cell intrinsic activity is essential for regulating dendrite growth, establishing connections with cerebellar nuclei, and ensuring proper cerebellar function. Disrupting this activity during the postnatal period impairs motor function, with earlier disruptions causing more severe effects. Importantly, only disruptions during early development lead to pronounced defects in cellular morphology, highlighting key temporal windows for dendritic growth and maturation. Transcriptomic analysis revealed that early intrinsic activity drives the expression of activity-dependent genes, such as Prkcg and Car8, which are essential for dendritic growth. Our findings emphasize the importance of temporally-specific intrinsic activity in Purkinje cells for guiding cerebellar circuit development, providing a potential common mechanism underlying cerebellum-related disorders.

neuroscience↗

bioRxiv2024

Prenatal tuning of thalamic spontaneous activity patterns regulates somatosensory map resolution

Precise mapping of peripheral inputs onto cortical areas is required for appropriate sensory processing. In the mouse primary somatosensory cortex, mystacial whiskers are represented in large barrels, while upper lip whiskers are in smaller, less defined barrels. Barrel size and definition of these two functionally distinct barrel maps are believed to be determined by the type of whisker input and peripheral receptor density. However, spontaneous activity and transcriptional programs at prenatal developmental stages can influence somatosensory map development independently of sensory experience. Thus, the mechanisms defining distinct barrel field territories, including their size and definition, remain poorly understood. Here, we show that prenatal ablation of mystacial whiskers remap somatosensory cortical territories resulting in enhancement of the functional and anatomical definition of upper lip whisker barrels. These changes do not result from alterations in receptor type but rather stem from thalamic upper lip input-receiving neurons adopting a mystacial-like transcriptional profile. Our results unveil a regulated prenatal mechanism within the thalamus that maps available somatosensory input to ensure sufficient cortical barrel size and functional spatial resolution for sensory processing, irrespective of peripheral receptor type and density.

neuroscience↗

bioRxiv2020

Thalamic spontaneous activity coordinates the timing of corticothalamic innervation in the visual system

Sensory processing relies on the correct development of thalamocortical loops. Visual corticothalamic axons (CTAs) invade the dorsolateral geniculate nucleus (dLGN) of the thalamus in early postnatal mice according to a regulated program that includes activity-dependent mechanisms. Spontaneous retinal activity influences the thalamic incursion of CTAs, yet the perinatal thalamus also generates intrinsic patterns of spontaneous activity whose role in modulating afferent connectivity remains unknown. Here, we found that patterned spontaneous activity in the dLGN contributes to proper spatial and temporal innervation of CTAs. Disrupting patterned spontaneous activity in the dLGN delays corticogeniculate innervation under normal conditions and upon eye enucleation. The delayed innervation was evident throughout the first two postnatal weeks but resumes after eye-opening, suggesting that visual experience is necessary for the homeostatic recovery of corticogeniculate innervation.

neuroscience↗

bioRxiv2020

Astrocytes and neurons share brain region-specific transcriptional signatures

Neuronal cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterised by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and glia. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis revealed the existence of common nucleus-specific progenitors for neurons and glia. Consistent with their shared molecular signature, regional specificity was maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.

neuroscience↗