Biology subjects

Labusch, M.

Publications and source records attributed to Labusch, M..

3 recordsLinked to original sources

bioRxiv2023

Prosaposin maintains adult neural stem cells in a state associated with deep quiescence

In most vertebrates, adult neural stem cells (NSCs) continuously give rise to neurons in discrete brain regions. A critical process for maintaining NSC pools over long periods of time in the adult brain is NSC quiescence, a reversible and tightly regulated state of cell cycle arrest. Recently, lysosomes were identified to regulate the NSC quiescence-proliferation balance. However, it remains controversial whether lysosomal activity promotes NSC proliferation or quiescence, and a finer influence of lysosomal activity on NSC quiescence duration or depth remains unexplored. Using RNA-sequencing and pharmacological manipulations, we show that lysosomes are necessary for NSC quiescence maintenance. Additionally, we reveal that expression of psap, encoding the lysosomal regulator Prosaposin, is enriched in quiescent NSCs (qNSCs) that reside upstream in the NSC lineage and display a deep/long quiescence phase in the adult zebrafish telencephalon. We show that shRNA-mediated psap knock-down increases the proportion of activated NSCs (aNSCs) as well as NSCs that reside in shallower quiescence states (signed by ascl1a and deltaA expression). Collectively, our results identify the lysosomal protein Psap as a (direct or indirect) quiescence regulator and unfold the interplay between lysosomal function and NSC quiescence heterogeneities.

neuroscience↗

bioRxiv2022

Apical size and deltaA expression predict adult neural stem cell decisions along lineage progression

The maintenance of neural stem cells (NSCs) in the adult brain depends on their activation frequency and division mode. We use long-term intravital imaging of NSCs in the zebrafish adult telencephalon to link activation and division mode with predictive cellular and molecular parameters. We reveal that apical surface area and expression of the Notch ligand DeltaA predict NSC activation frequency, while deltaA expression marks NSC commitment to neurogenesis. We also find that deltaA-negative NSCs constitute the bona fide self-renewing NSC pool and systematically engage in asymmetric divisions generating a self-renewing deltaAneg and a neurogenic deltaApos NSC. Finally, modulation of Notch signaling during imaging indicates that the prediction of activation frequency by apical size, and the asymmetric divisions of deltaAneg NSCs, are functionally independent of Notch. These results provide dynamic qualitative and quantitative readouts of NSC lineage progression in vivo and support a hierarchical organization of NSCs in differently fated sub-populations.

neuroscience↗

bioRxiv2019

Mosaic heterochrony in neural progenitors sustains accelerated brain growth and neurogenesis in the juvenile killifish N. furzeri

While developmental mechanisms driving increase in brain size during vertebrate evolution are actively studied, we know less of evolutionary strategies allowing to boost brain growth speed. In zebrafish and other vertebrates studied to date, radial glia (RG) constitute the primary neurogenic progenitor population throughout life (Kriegstein and Alvarez-Buylla, 2009); thus, RG activity is a determining factor of growth speed. Here, we ask whether enhanced RG activity is the mechanism selected to drive explosive growth, in adaptation to an ephemeral habitat. In post-hatching larvae of the turquoise killifish, which display drastic developmental acceleration, we show that the dorsal telencephalon (pallium) grows three times faster than in zebrafish. Rather than resulting from enhanced RG activity, we demonstrate that pallial growth is the product of a second type of progenitors (that we term AP for apical progenitors) that actively sustains neurogenesis and germinal zone self-renewal. Intriguingly, AP appear to retain, at larval stages, features of early embryonic progenitors. In parallel, RG enter premature quiescence and express markers of astroglial function. Together, we propose that mosaic heterochrony within the neural progenitor population may permit rapid pallial growth by safeguarding both continued neurogenesis and astroglial function.

developmental biology↗