Biology subjects

Paridaen, J. T. M. L.

Publications and source records attributed to Paridaen, J. T. M. L..

4 recordsLinked to original sources

bioRxiv2024

Developmental emergence of quiescent-like neural progenitor cells in the zebrafish embryonic brain

The mature brain is made up of differentiated neurons and glial cells that are produced by embryonic neural stem and progenitor cells (collectively called neural stem cells (NSCs)) during brain development. In contrast, adult NSCs generate only a limited number of neuronal and glial cell types. Moreover, in contrast to embryonic NSCs, adult NSCs spend most of their time in a non-dividing resting phase called quiescence. In the adult brain, the quiescent NSCs are activated at a low frequency to divide and produce new cells to replace lost or damaged mature cells. Previous studies have demonstrated that about halfway through mammalian brain development, a subset of the embryonic NSCs population slows down their division rate and slowly transition into adult quiescent NSCs (qNSCs). However, the molecular mechanisms that underlie the emergence of the pre-adult SCs remain largely unknown. Here, we explored single-cell transcriptomes from several embryonic stages of zebrafish development in order to determine at what developmental stage transcriptional signatures typical of adult quiescent NSCs first emerge. We identified a subpopulation of embryonic NSCs with a distinct transcriptional profile from other embryonic NSCs. This population shares transcriptional similarities with adult qNSCs including genes known to maintain quiescence. We propose that this population constitute slower cycling embryonic NSCs that may transition into the adult qNSCs of the adult zebrafish brain.

developmental biology↗

bioRxiv2023

A quantitative characterization of early neuron generation in the developing zebrafish telencephalon.

The adult brain is made up of anatomically and functionally distinct regions with specific neuronal compositions. At the root of this neuronal diversity are neural stem and progenitor cells (NPCs) that produce many neurons throughout embryonic development. During development, NPCs switch from initial expanding divisions to neurogenic divisions, which marks the onset of neurogenesis. Here, we aimed to understand when NPCs switch division modes to generate the first neurons in the anterior-most part of the zebrafish brain, the telencephalon. To this end, we used the deep learning-based segmentation method Cellpose and clonal analysis of individual NPCs to assess production of neurons by NPCs in the first 24 hours of zebrafish telencephalon development. Our results provide a quantitative atlas detailing the production of telencephalic neurons and NPC division modes between 14 and 24 hours post-fertilization. We find that within this timeframe, the switch to neurogenesis is gradual, with considerable heterogeneity in individual NPC neurogenic potential and division rates. This quantitative characterization of initial neurogenesis in the zebrafish telencephalon establishes a basis for future studies aimed at illuminating the molecular mechanisms and regulators of early neurogenesis.

developmental biology↗

bioRxiv2021

The developmental stage of the medulloblastoma cell-of-origin restricts Hedgehog pathway usage and drug sensitivity

Sonic Hedgehog (SHH) medulloblastoma originates from the cerebellar granule neuron progenitor (CGNP) lineage that depends on Hedgehog signaling for its perinatal expansion. While SHH tumors exhibit overall deregulation of this pathway, they also show patient age-specific aberrations. To investigate if the developmental stage of the CGNP can account for these age-specific lesions, we analyzed developing murine CGNP transcriptomes and observed highly dynamic gene expression as function of age. Cross-species comparison with human SHH medulloblastoma showed partial maintenance of these expression patterns, and highlighted low primary cilium expression as hallmark of infant medulloblastoma and early embryonic CGNPs. This coincided with reduced responsiveness to upstream Shh pathway component Smoothened, while sensitivity to downstream components Sufu and Gli was retained. Together, these findings can explain the preference for SUFU mutations in infant medulloblastoma and suggest that drugs targeting the downstream SHH pathway will be most appropriate for infant patients.

cancer biology↗

bioRxiv2018

YAP activity is necessary and sufficient for basal progenitor abundance and proliferation in the developing neocortex

The expansion of the neocortex during mammalian evolution has been linked to an enlargement of the subventricular zone during cortical development and an increase in the proliferation of the basal progenitors residing therein. Here, we explored a potential role of YAP, the major downstream effector of the Hippo signaling pathway, in proliferation of basal progenitors. We show that YAP expression and activity are high in ferret and human basal progenitors, which are known to exhibit high proliferative capacity, but low in mouse basal progenitors, which lack such capacity. To induce YAP activity in mouse basal progenitors, we expressed a constitutively active YAP (CA-YAP). This resulted in an increase in proliferation of basal progenitor. In addition, CA-YAP expressing mouse basal progenitors promoted the production of upper-layer neurons. To investigate if YAP is required for the proliferation of basal progenitors, we pharmacologically interfered with the function of YAP in the developing ferret and human neocortex. This resulted in a decrease of cycling basal progenitors. In concert, genetical interference with the function of YAP in ferret developing neocortex resulted in decreased abundance of basal progenitors. Together, our data indicate that YAP promotes the proliferation of basal progenitors and suggest that changes in YAP activity levels contributed to the evolutionary expansion of the neocortex.

neuroscience↗