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

Abstract

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.

Conserved and Divergent Features of Adult Neurogenesis in Zebrafish

“…As a response to its ephemeral habitat, N. furzeri follows an explosive development to its adult size (Blažek et al, 2013), including accelerated pallial growth and neurogenesis. Recent work demonstrates that this is not due to the enhanced efficiency of existing lineages, but rather to the long-term persistence until adulthood of a highly neurogenic embryonic lineage ( Figure 2B; Coolen et al, 2020). This study, which points to the variety of neurogenic adaptations in the adult vertebrate brain, illustrates the power of fish models to uncover the different natural strategies that can be used to amplify neurogenesis.…”

“…(B) Lineages in the killifish, where neurogenesis in adults is ensured by a long-lasting non-glial embryonic lineage (blue) dph: days post-hatching, wph: weeks post-hatching. (C) Lineages in mouse, where distinct modes of NSC production are described in the DG (top) and SEZ (bottom) (Dirian et al, 2014;Furutachi et al, 2015;Song et al, 2018;Berg et al, 2019;Coolen et al, 2020).…”

Radial glia in the zebrafish brain: Functional, structural, and physiological comparison with the mammalian glia

“…Finally, lineage‐tracing experiments revealed that the heterogenous adult neural stem cells are hierarchically organized into deeply quiescent and self‐renewing reservoir stem cells supporting constitutive neurogenesis across the zebrafish life (Than‐Trong et al, 2020). Recently, a fast‐growing teleost fish N. furzerii (killifish) was shown to contain non‐glial progenitors that are rapidly dividing and contributing the quick growth of the brain (Coolen, Labusch, Mannioui, & Bally‐Cuif, 2020). Non‐glial progenitors were suggested to delay their entry into the quiescence and therefore can contribute to the fast growth needed for the short‐living killifish (Coolen et al, 2020).…”

“…Recently, a fast‐growing teleost fish N. furzerii (killifish) was shown to contain non‐glial progenitors that are rapidly dividing and contributing the quick growth of the brain (Coolen, Labusch, Mannioui, & Bally‐Cuif, 2020). Non‐glial progenitors were suggested to delay their entry into the quiescence and therefore can contribute to the fast growth needed for the short‐living killifish (Coolen et al, 2020). Such heterochrony of neural progenitors might be an underlying determining factor for the neurogenic and regenerative properties of the teleost brains, and can be instrumental in understanding the balance between quiescence and proliferation in health and disease.…”

Aging impairs the essential contributions of non‐glial progenitors to neurorepair in the dorsal telencephalon of the Killifish Nothobranchius furzeri

“…It was recently discovered that the killifish dorsal pallium holds two classes of progenitors: (1) the commonly known radial glia (RGs) and (2) the non‐glial progenitors (NGPs). NGPs are devoid of the typical astroglial/RG markers, such as glutamine synthetase (GS), brain lipid‐binding protein (BLBP), glial fibrillary acidic protein (GFAP), and vimentin, and have a morphology that is less branched than RGs (Coolen et al, 2020). Early in development, killifish RGs enter a premature quiescent state and proliferation is supported by the NGPs.…”