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Harris, A.

Publications and source records attributed to Harris, A..

3 recordsLinked to original sources

Onecut factors and Pou2f2 regulate diversification and migration of V2 interneurons in the mouse developing spinal cord

Acquisition of proper neuronal identity and position is critical for the formation of neural circuits. In the embryonic spinal cord, cardinal populations of interneurons diversify into specialized subsets and migrate to defined locations within the spinal parenchyma. However, the factors that control interneuron diversification and migration remain poorly characterized. Here, we show that the Onecut transcription factors are necessary for proper diversification and distribution of the V2 interneurons in the developing spinal cord. Furthermore, we uncover that these proteins restrict and moderate the expression of spinal isoforms of Pou2f2, a transcription factor known to regulate B-cell differentiation. By gain- or loss-of-function experiments, we show that Pou2f2 contribute to regulate the position of V2 populations in the developing spinal cord. Thus, we uncovered a genetic pathway that regulates the diversification and the distribution of V2 interneurons during embryonic development.\n\nSignificance statementIn this study, we identify the Onecut and Pou2f2 transcription factors as regulators of spinal interneuron diversification and migration, two events that are critical for proper CNS development.

developmental biology

Accounting for taste: A multi-attribute neurocomputational model explains the neural dynamics of choices for self and others

How do we make choices for others with different preferences from our own? Although neuroimaging studies implicate similar circuits in representing preferences for oneself and others, some models propose that additional corrective mechanisms come online when choices for others diverge from ones own preferences. Here we used event-related potentials (ERP) in humans, in combination with computational modeling, to examine how social information is integrated in the time leading up to choices for oneself and others. Hungry male and female participants with unrestricted diets selected foods for themselves, a similar unrestricted eater, and a dissimilar, self-identified healthy eater. Across choices for both oneself and others, ERP value signals emerged within the same time window but differentially reflected taste and health attributes based on the recipients preferences. Choices for the dissimilar recipient were associated with earlier activity localized to brain regions implicated in social cognition including temporoparietal junction (TPJ). Finally, response-locked analysis revealed a late ERP component specific to choices for the similar recipient, localized to the parietal lobe, that appeared to reflect differences in the response threshold based on uncertainty. A multi-attribute computational model supported the link between specific ERP components and distinct model parameters, and was not significantly improved by adding time-dependent dual processes. Model simulations suggested that longer response times (RTs) previously associated with effortful correction may alternatively arise from higher choice uncertainty. Together these results provide a parsimonious neurocomputational mechanism for social decision-making, additionally explaining divergent patterns of choice and RT data in decisions for oneself and others.\n\nSignificance StatementHow do we choose for others, particularly when they have different preferences? Whereas some studies suggest that similar neural circuits underlie decision-making for oneself and others, others argue for additional, slower perspective-taking mechanisms. Combining event-related potentials with computational modeling, we found that integration of others preferences occurs over the same timescale as for oneself, while differentially tracking recipient-relevant attributes. Although choosing for others took longer and produced differences in late-emerging neural responses, computational modeling attributed these patterns to greater response caution rather than egocentric bias correction. Computational simulations also correctly predicted when and why choosing differently for others takes longer, suggesting that a model incorporating value integration and evidence accumulation can parsimoniously account for complex patterns in social decision-making.

neuroscience

Stress relaxation in epithelial monolayers is controlled by actomyosin

Epithelial monolayers are one-cell thick tissue sheets that separate internal and external environments. As part of their function, they withstand extrinsic mechanical stresses applied at high strain rate. However, little is known about how monolayers respond to mechanical deformations. In stress relaxation tests, monolayers respond in a biphasic manner and stress dissipation is accompanied by an increase in monolayer resting length, pointing to active remodelling of cell architecture during relaxation. Consistent with this, actomyosin remodels at a rate commensurate with mechanical relaxation and governs the rate of monolayer stress relaxation - as in single cells. By contrast, junctional complexes and intermediate filaments form stable connections between cells, enabling monolayers to behave rheologically as single cells. Together, these data show actomyosin cytoskeletal dynamics govern the rheological properties of monolayers by enabling active, ATP-dependent changes in the resting length. These findings have far-reaching consequences for our understanding of developmental morphogenesis and tissue response to mechanical stress.

biophysics