Biology subjects

Touboul, J.

Publications and source records attributed to Touboul, J..

4 recordsLinked to original sources

bioRxiv2018

Symmetry breaking in the embryonic skin triggers a directional and sequential front of competence during plumage patterning

The development of an organism involves the formation of patterns from initially homogeneous surfaces in a reproducible manner. Simulations of various theoretical models recapitulate final states of natural patterns1-4 yet drawing testable hypotheses from those often remains difficult4,5. Consequently, little is known on pattern-forming events. Here, we extend modeling to reproduce not only the final plumage pattern of birds, but also the observed natural variation in its dynamics of emergence in five species. We built a unified model intrinsically generating the directionality, sequence, and duration of patterning, and used in vivo experiments to test its parameter-based predictions. We showed that while patterning duration is controlled by overall cell proliferation, its directional and sequential progression result from a pre-pattern: an initial break in surface symmetry launches a traveling front of increased cell density that defines domains with self-organizing capacity. These results show that universal mechanisms combining pre-patterning and self-organization govern the timely emergence of the plumage pattern in birds.

developmental biology↗

bioRxiv2018

Opto-activation of cortical somatostatin interneurons alleviates parkinsonian symptoms

Deep brain stimulation of the subthalamic nucleus is a symptomatic treatment of Parkinsons disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics and modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A mathematical model highlights how the decrease in pyramidal neurons activity can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.\n\nOne-sentence SummaryDeep brain stimulation recruits cortical somatostatin interneurons, and their opto-activation is beneficial in Parkinsons.

neuroscience↗

bioRxiv2018

In vitro characterization of the human segmentation clock

The vertebral column is characterized by the periodic arrangement of vertebrae along the anterior-posterior (AP) axis. This segmental or metameric organization is established early in embryogenesis when pairs of embryonic segments called somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock 1,2. While this oscillator has been well characterized in model organisms 1,2, whether a similar oscillator exists in humans remains unknown. We have previously shown that human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells can differentiate in vitro into PSM upon activation of the Wnt signaling pathway combined with BMP inhibition3. Here, we show that these human PSM cells exhibit Notch and YAP-dependent oscillations4 of the cyclic gene HES7 with a 5-hour period. Single cell RNA-sequencing comparison of the differentiating iPS cells with mouse PSM reveals that human PSM cells follow a similar differentiation path and exhibit a remarkably coordinated differentiation sequence. We also demonstrate that FGF signaling controls the phase and period of the oscillator. This contrasts with classical segmentation models such as the \"Clock and Wavefront\" 1,2,5, where FGF merely implements a signaling threshold specifying where oscillations stop. Overall, our work identifying the human segmentation clock represents an important breakthrough for human developmental biology.

developmental biology↗

bioRxiv2018

Development of inhibitory synaptic delay drives maturation of thalamocortical network dynamics

Nervous system maturation occurs on multiple levels, synaptic, circuit, and network, at divergent time scales. For example, many synaptic properties mature gradually, while emergent network dynamics, as data show, change abruptly. Here, we combine experimental and theoretical approaches to investigate a sudden transition in spontaneous thalamocortical activity necessary for the development of vision. Inspired by in vivo measurements of time-scales and amplitudes of synaptic currents, we extend the Wilson and Cowan model to take into account the relative onset timing and amplitudes of inhibitory and excitatory neural population responses. We study the dynamics of this system and identify the bifurcations as the onset timescales of excitation and inhibition are varied. We focus on the specific typical developmental changes in synaptic timescales consistent with the experimental observations. These findings argue that the inhibitory timing is a critical determinant of thalamocortical activity maturation; a gradual decay of the ratio of inhibitory to excitatory onset time below one drives the system through a bifurcation that leads to a sudden switch of the network spontaneous activity from high-amplitude oscillations to a non-oscillatory active state. This switch also drives a marked change to a linear network response to transient stimuli, agreeing to the in vivo observations. The switch observed in the model is representative of the sudden transition in the sensory cortical activity seen early in development.

neuroscience↗