Biology subjects

Sabate San Jose, A.

Publications and source records attributed to Sabate San Jose, A..

3 recordsLinked to original sources

bioRxiv2024

Evidence that Dmrta2 acts as a transcriptional repressor of Pax6 in murine cortical progenitors and identification of a mutation crucial for DNA recognition associated with microcephaly in human

Dmrta2 (also designated Dmrt5) is a transcriptional regulator expressed in cortical progenitors in a caudomedialhigh/rostrolaterallow gradient with important roles at different steps of cortical development. Dmrta2 has been suggested to act in cortex development mainly by differential suppression of Pax6 and other homeobox transcription factors such as the ventral telencephalic regulator Gsx2, which remains to be fully demonstrated. Here we have addressed the epistatic relation between Pax6 and Dmrta2 by comparing phenotypes in mutant embryos or embryos overexpressing both genes in various allelic combinations. We showed that Dmrta2 cooperates with Pax6 in the maintenance of cortical identity in dorsal telencephalic progenitors and that it acts as a transcriptional repressor of Pax6 to control cortical patterning. Mechanistically, we show that in P19 cells, Dmrta2 can act as a DNA-binding dependent repressor on the Pax6 E60 enhancer and that a point mutation that affects its DNA binding properties leads to agenesis of the corpus callosum, pachygyria, and the absence of the cingulate gyrus. Finally, we provide evidence that Dmrta2 binds to the Zfp423 zinc finger protein and that it enhances its ability to recruit the NurD repressor complex. Together, our results highlight the importance and conserved function of Dmrta2 in cortical development and provide novel insights into its mechanism of action. SIGNIFICANCE STATEMENTCorticogenesis is controlled by an array of transcription factors that coordinate neural progenitor self-renewal and differentiation to generate correct cortical cell number and diversity. However, how this complex array of transcription factors works in concert to regulate this delicate process remains largely unknown. Here we provide important insights into the mechanism of action of Dmrta2 by demonstrating that it cooperates with the transcription factor Pax6 to define the pallium-subpallium boundary and that it acts by repressing it, likely via the recruitment of Zfp423 and the NurD repressor complex, to control cortical patterning. Our data also reveal that a point mutation that affects its DNA binding causes cortical abnormalities in human, further highlighting its importance in cortex development.

neuroscience↗

bioRxiv2024

The temporal refinement of Dach1 is a key step in the functional maturation of primary somatosensory neurons

During somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state, with several transcription factors following a broad-to-restricted expression dynamic as development proceeds, supporting neuron subtype identities. The relevance of this temporal refinement remains however unclear, these broad-to-restricted transcription factors being selectively involved in neurons in which they are ultimately maintained. Here we found that Dach1 encodes for a bona fide broad-to-restricted transcription factor retained and required in tactile somatosensory neurons. Within developing nociceptors, we demonstrate that Prdm12 contributes to Dach1 extinction. Using genetic approaches to prevent its temporal restriction during somatosensory development, we reveal that Dach1 refinement is a prerequisite for the appropriate transcriptional maturation of somatosensory subtypes from which it becomes ultimately excluded. These findings highlight the essential role played by Dach1 during somatosensory neuron development. They further demonstrate that the broad-to-restricted temporal pattern followed by several transcription factors is physiologically relevant to achieve appropriate transcriptional maturation of somatosensory neurons.

neuroscience↗

bioRxiv2020

Alpha fluctuations regulate the accrual of visual information to awareness

Endogenous brain processes play a paramount role in shaping up perceptual phenomenology. This is illustrated by the alternations experienced by humans (and other animals) when watching perceptually ambiguous, static images. We hypothesised that endogenous alpha fluctuations in the visual cortex pace the accumulation of sensory information leading to perceptual outcomes. Here, we addressed this hypothesis using binocular rivalry combined with visual entrainment and electroencephalography in humans (64 female, 53 male). The results revealed a correlation between the individual frequency of alpha oscillations in the occipital cortex and perceptual alternation rates experienced during binocular rivalry. In subsequent experiments we show that regulating endogenous brain activity via rhythmic entrainment produced corresponding changes in perceptual alternation rate. These changes were observed only in the alpha range but not at lower entrainment frequencies, and were much reduced when using arrhythmic stimulation. Additionally, entraining at frequencies above the alpha range did not result in speeding up perceptual alternation rates. Overall, these findings support the notion that visual information is accumulated via alpha cycles to promote the emergence of conscious perceptual representations. We suggest that models of binocular rivalry incorporating posterior alpha as a pacemaker can provide an important advance in the comprehension of the dynamics of visual awareness.

neuroscience↗