Biology subjects

Hevia, C. F.

Publications and source records attributed to Hevia, C. F..

3 recordsLinked to original sources

bioRxiv2024

Her9 controls the stemness properties of the hindbrain boundary cells

Different spatiotemporal distribution of progenitor/neurogenic capacities permits that brain regions engage asynchronously in neurogenesis. In the hindbrain, rhombomere progenitor cells are the main contributors to neurons during the first neurogenic phase, whereas boundary cells participate later, relying on Notch3-activity. To analyze the mechanism(s) that maintain boundary cells as proliferative progenitors not engaging in neurogenesis, we addressed the role of the zebrafish Hes1 ortholog, Her9, in this cell population. her9 expression is temporarily sustained in boundary cells in a Notch-independent manner while they behave as non-neurogenic progenitors. Functional manipulations demonstrate that Her9 inhibits the onset of Notch-signaling and the neurogenic program, thus keeping boundary cells in the progenitor state. Combining multicolor clonal analysis with functional approaches, we reveal a role of Her9 in the expansion of boundary progenitors by promoting symmetric proliferative divisions and preventing neurogenic cell divisions. Moreover, Her9 regulates the proliferation of boundary cells by inhibiting the cell cycle gene cdkn1ca and potentially interplaying with CyclinD1. Altogether, Her9 maintains the stemness and proliferation of hindbrain boundary progenitors at early embryonic stages.

developmental biology↗

bioRxiv2021

The neurogenic fate of the hindbrain boundaries: a Notch-dependent behavioral switch triggers asymmetric division of boundary stem cells

The generation of cell diversity in the central nervous system occurs during embryogenesis and requires a precise balance between cell proliferation, commitment to specific fates, and further neuronal differentiation. The cellular and molecular mechanisms regulating this balance in the embryonic brain are still poorly understood. Here we study how the neurogenic capacity in the embryonic hindbrain is spatiotemporally allocated, and how the fate and the growth of the hindbrain boundary cells are regulated. By generating a CRISPR-based knock-in zebrafish transgenic line to specifically label the hindbrain boundaries, we unveiled that boundary cells undergo a functional transition to become neurogenic during hindbrain segmentation concurrently as they maintain the progenitor cell pool. Boundary cells engaged in neurogenesis coinciding with the onset of Notch signaling, which triggered their asymmetrical cell division. Our findings reveal that distinct neurogenic phases take place during hindbrain growth and suggest that boundary cells contribute to refine the final number, identity, and proportion of neurons in the brain. SUMMARYHindbrain boundary cells undergo a functional transition to become neurogenic concurrently as they are maintained as a progenitor cell pool. This involves a behavioral switch from symmetrically dividing progenitor cells to asymmetrically dividing progenitors, which depends on Notch-activity.

developmental biology↗

bioRxiv2018

YAP/TAZ-TEAD Activity Links Mechanical Cues To Specific Cell Fate Within The Hindbrain Boundaries

Cells perceive their microenvironment through chemical and physical cues. However, how mechanical signals are interpreted during embryonic tissue deformation resulting in specific cell behaviors is largely unexplored. The Yap/Taz family of transcriptional co-activators has emerged as an important regulator of tissue growth and regeneration, responding to physical cues from the extracellular matrix, cell shape and actomyosin cytoskeleton. In this work, we unveiled the role of Yap/Taz-TEAD activity as sensor of mechanical signals in the regulation of the progenitor behavior of boundary cells during hindbrain compartmentalization. Monitoring in vivo Yap/Taz-activity during hindbrain segmentation we discovered that boundary cells respond to mechanical cues in a cell-autonomous manner through Yap/Taz-TEAD activity. Cell-lineage analysis revealed that Yap/Taz-TEAD boundary cells decrease their proliferative activity when Yap/Taz-TEAD ceased, preceding changes of cell fate: from proliferating progenitors to differentiated neurons. Functional experiments demonstrated the pivotal role of Yap/Taz-TEAD signaling in maintaining the progenitor features in the hindbrain boundary cell population.

developmental biology↗