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Avalos, C. B.

Publications and source records attributed to Avalos, C. B..

3 recordsLinked to original sources

Post-translational Tuning of Human Cortical Progenitor Neuronal Output

The striking expansion of the human neocortex is driven by the ability of radial glial cells (RGCs) to prolong neurogenesis without exhausting their progenitor pool, thereby producing more neurons, particularly in the upper layers. The mechanisms underlying enhanced human neurogenic output remain unresolved. We hypothesized that post-translational modification of conserved proteins could provide a flexible mechanism supporting species-specific patterns of neurogenesis. Here, we identify phosphorylation of the proneural factor NEUROGENIN2 as a regulator of human RGC neuronal output by modulating its pioneering-like activity, at the expense of its transactivation function. This, in turn, remodels the RGC chromatin landscape, resulting in a forward temporal shift of RGC gene regulatory networks and leading to increased neuronal production biased towards upper-layer neurons. Our work proposes a conceptual framework for how subtle modifications of conserved processes, and not just new genes, encode tunable mechanisms for species-specific trajectories of brain development.

developmental biology↗

Food texture preference reveals multisensory contributions of gustatory organs in behaviour and physiology

Food presents a multisensory experience, with visual, taste, and olfactory cues being important in allowing an animal to determine the safety and nutritional value of a given substance1. Texture, however, remains a surprisingly unexplored aspect, despite providing key information about the state of the food through properties such as hardness, liquidity, and granularity. Food perception is achieved by specialised sensory neurons, which themselves are defined by the receptor genes they express. While it was assumed that sensory neurons respond to one or few closely-related stimuli, more recent findings challenge this notion and support evidence that certain sensory neurons are more broadly tuned. In the Drosophila taste system, gustatory neurons respond to cues of opposing hedonic valence or to olfactory cues. Here, we identified that larvae ingest and navigate towards specific food substrate hardnesses, and probed the role of gustatory organs in this behaviour. By developing a genetic tool targeting specifically gustatory organs, we show that these organs are major contributors for evaluation of food texture and ingestion decision-making. We find that ablation of gustatory organs not only results in loss of chemosensation, but also navigation and ingestion preference to varied substrate textures. Furthermore, we show that certain neurons in the primary taste organ exhibit varied and concurrent physiological responses to mechanical and multimodal stimulation. We show that individual neurons house independent mechanisms for multiple sensory modalities, challenging assumptions about capabilities of sensory neurons. We propose that further investigations, across the animal kingdom, may reveal higher sensory complexity than currently anticipated.

neuroscience↗

A cell fate decision map reveals abundant direct neurogenesis in the human developing neocortex

The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial (bRG) cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remains unknown. Here, we developed a semi-automated live/fixed correlative imaging method to generate a map of bRG cell division modes in early fetal tissue and cerebral organoids. Through the analysis of over 1,000 dividing progenitors, we show that bRG cells undergo abundant symmetric amplifying divisions, followed by frequent direct neurogenic divisions, bypassing intermediate progenitors. These direct neurogenic divisions are more abundant in the upper part of the subventricular zone. We furthermore demonstrate asymmetric Notch activation in the self-renewing daughter cells, independently of basal fiber inheritance. Our results reveal a remarkable conservation of fate decisions in cerebral organoids, supporting their value as models of early human neurogenesis.

developmental biology↗