S‐phase duration is the main target of cell cycle regulation in neural progenitors of developing ferret neocortex

García, Miguel Turrero; Chang, YoonJeung; Arai, Yoko; Huttner, Wieland B.

doi:10.1002/cne.23801

Cited by 56 publications

(49 citation statements)

References 51 publications

(134 reference statements)

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“…Interestingly, similar changes in cell cycle have been observed in Axolotls, suggesting that it might be a general principle of spinal cord regeneration [8,21]. It has been suggested that long S phase might be necessary for progenitors undergoing selfrenewal division to ensure genome integrity, especially in response to high level of ROS present in the nervous system [22][23][24]. The regenerating tail is an oxidative environment and we show here that foxm1 expression requires ROS.…”

Section: Discussionsupporting

confidence: 75%

Foxm1 regulates neuronal progenitor fate during spinal cord regeneration

Pelzer¹,

Phipps

Thuret³

et al. 2020

Preprint

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Keywords: spinal cord / regeneration / Foxm1 / progenitor / Xenopus / differentiation Pelzer et al. Role of Foxm1 during spinal cord regeneration 2 Summary Mammals have limited tissue regeneration capabilities, particularly in the case of the central nervous system. Spinal cord injuries are often irreversible and lead to the loss of motor and sensory function below the site of the damage [1]. In contrast, amphibians suchas Xenopus tadpoles can regenerate a fully functional tail, including their spinal cord, following amputation [2,3]. A hallmark of spinal cord regeneration is the re-activation of Sox2/3+ progenitor cells to promote regrowth of the spinal cord and the generation of new neurons [4,5]. In axolotls, this increase in proliferation is tightly regulated as progenitors switch from a neurogenic to a proliferative division via the planar polarity pathway (PCP) [6][7][8]. How the balance between self-renewal and differentiation is controlled during regeneration is not well understood. Here, we took an unbiased approach to identify regulators of the cell cycle expressed specifically in X.tropicalis spinal cord after tail amputation by RNAseq. This led to the identification of Foxm1 as a potential key transcription factor for spinal cord regeneration. Foxm1-/-X.tropicalis tadpoles develop normally but cannot regenerate their spinal cords. Using single cell RNAseq and immunolabelling, we show that foxm1+ cells in the regenerating spinal cord undergo a transient but dramatic change in the relative length of the different phases of the cell cycle, suggesting a change in their ability to differentiate. Indeed, we show that Foxm1 does not regulate the rate of progenitor proliferation but is required for neuronal differentiation leading to successful spinal cord regeneration. Pelzer et al. Role of Foxm1 during spinal cord regeneration 3 Results Foxm1 is specifically expressed in the regenerating spinal cordWe compared the transcriptome of isolated spinal cords at 1day post amputation (1dpa) and 3dpa to spinal cord from intact tails (0dpa, Figure 1A). Principle component plot, dendogram of sample-to-sample distances and MA-plot of the log fold change (FC) of expression in relation to the average count confirmed the quality of the data (Figures S1A-D). Between 0dpa and 1dpa, 5129 differentially expressed (DE) transcripts (FC> 2 and FDR<0.01) were identified (2074 down-, 3055 up-regulated). Between 0dpa and 3dpa, 9787 genes are differentially expressed (4609 down and 5178 up-regulated, Figure S1E).To identify the most enriched biological processes by gene ontology (GO), a nonbiased hierarchical cluster for all DE genes was performed ( Figure 1B). We observed three phases: first an increase in expression of genes involved in metabolic processes (cluster I), then a strong upregulation of genes associated with cell cycle regulation (cluster II and III) and finally, a downregulation of expression of genes involved in nervous system development (Cluster IV and V, Figure 1B).Using Ingenuity Pathway Analysis (IPA), we identi...

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Section: Discussionsupporting

confidence: 75%

Foxm1 regulates neuronal progenitor fate during spinal cord regeneration

Pelzer¹,

Phipps

Thuret³

et al. 2020

Preprint

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“…The cell cycle length of the dividing cells of the adult rat DG was estimated to be 25h, of which 9.7h was the length of the S‐phase (Cameron & McKay, ). Even if studies on the cell cycle length of the canine neural dividing cells are lacking, the S‐phase length of neural progenitors of non‐human primates and ferrets (gyrencephalic carnivore animals) was found to be less than 24h (Kornack & Rakic, ; Turrero Garcia et al, ), allowing us to infer that the extremely low difference (less than 14h) in the S‐phase length of the carnivore and rodent neural progenitors could affect only the short‐term outcome of the ongoing neurogenesis and could not have any effect in the here long‐term study of the rat and canine BrdU + cell populations.…”

Section: Discussionmentioning

confidence: 98%

“…Current literature proposes a lengthened cell cycle and particularly an extended S‐phase for proliferating neural cells of the gyrencephalic brains as compared to the rodent ones (Turrero Garcia et al, ). The cell cycle length of the dividing cells of the adult rat DG was estimated to be 25h, of which 9.7h was the length of the S‐phase (Cameron & McKay, ).…”

Section: Discussionmentioning

confidence: 99%

Adult neurogenesis and gliogenesis in the dorsal and ventral canine hippocampus

Bekiari

Grivas

Tsingotjidou

et al. 2019

J of Comparative Neurology

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Dentate gyrus (DG) of the mammalian hippocampus gives rise to new neurons and astrocytes all through adulthood. Canine hippocampus presents many similarities in fetal development, anatomy, and physiology with human hippocampus, establishing canines as excellent animal models for the study of adult neurogenesis. In the present study, BrdU‐dated cells of the structurally and functionally dissociated dorsal (dDG) and ventral (vDG) adult canine DG were comparatively examined over a period of 30 days. Each part's neurogenic potential, radial glia‐like neural stem cells (NSCs) proliferation and differentiation, migration, and maturation of their progenies were evaluated at 2, 5, 14, and 30 days post BrdU administration, with the use of selected markers (glial fibrillary acidic protein, doublecortin, calretinin and calbindin). Co‐staining of BrdU+ cells with NeuN or S100B permitted the parallel study of the ongoing neurogenesis and gliogenesis. Our findings reveal the comparatively higher populations of residing granule cells, proliferating NSCs and BrdU+ neurons in the dDG, whereas newborn neurons of the vDG showed a prolonged differentiation, migration, and maturation. Newborn astrocytes were found all along the dorso‐ventral axis, counting however for only 11% of newborn cell population. Comparative evaluation of adult canine and rat neurogenesis revealed significant differences in the distribution of resident and newborn granule cells along the dorso‐ventral axis, division pattern of adult NSCs, maturation time plan of newborn neurons, and ongoing gliogenesis. Concluding, spatial and temporal features of adult canine neurogenesis are similar to that of other gyrencephalic species, including humans, and justify the comparative examination of adult neurogenesis across mammalian species.

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“…Indeed, overexpression of TRNP1 selectively increases aRG (and not bIPs), which results in tangential expansion of neocortex without gyrus formation . In ferrets, proliferating bRGs have a longer cell cycle duration (including a longer G1 and S phase) compared with the proliferating aRGs, which may result in greater contribution of the former cells to neurogenesis at late developmental stages and account for gyration . Altogether, these data support a critical contribution of intermediate progenitor proliferation to the formation of gyri.…”

Section: Cellular Bases Of Cortical Gyrationmentioning

confidence: 60%

Coupling progenitor and neuronal diversity in the developing neocortex

Govindan

Jabaudon

2017

FEBS Letters

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The adult neocortex is composed of several types of glutamatergic neurons, which are sequentially born from progenitors during development. The extent and nature of progenitor diversity, and how it relates to neuronal diversity, is still poorly understood. In this review, we discuss key features of neocortical progenitors across several species, including their morphological properties, cell cycling behaviour and molecular signatures, and how these features relate to the competence of these cells to generate distinct types of progenies. Keywords: neocortical development; neurogenesis; progenitor diversityThe adult neocortex is composed of several types of glutamatergic neurons, which assemble during development to form the circuits underlying many of our conscious perceptions and motor actions. These distinct neuronal subtypes are sequentially born from progenitors, but the extent and nature of progenitor diversity, and how it relates to neuronal diversity, is still poorly understood.Neocortical neurons are generated by progenitors located in the ventricular zone (VZ), which is located below the cortical plate (i.e. developing cortex) and lines the walls of the ventricles [1]. In mice, neurogenesis starts on the tenth embryonic day (E10.5) and proceeds for about a week, until E18.5, after which astrogliogenesis occurs (see Ref.[2] for a recent review). Early born neurons migrate to form the deepest cortical layers (layers 6 and 5) while later born neurons migrate past them to reside more superficially and form upper layers (layer 2, 3 and 4). Deep layer neurons mostly send their axons to subcortical targets such as the thalamus, hindbrain or spinal cord, while superficial layer neurons mostly project intracortically, either locally (layer 4 neurons), or by forming longrange intracortical and interhemispheric projections.

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S‐phase duration is the main target of cell cycle regulation in neural progenitors of developing ferret neocortex

Cited by 56 publications

References 51 publications

Foxm1 regulates neuronal progenitor fate during spinal cord regeneration

Foxm1 regulates neuronal progenitor fate during spinal cord regeneration

Adult neurogenesis and gliogenesis in the dorsal and ventral canine hippocampus

Coupling progenitor and neuronal diversity in the developing neocortex

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