Population Dynamics and Neuronal Polyploidy in the Developing Neocortex

Jungas, Thomas; Joseph, Mathieu; Fawal, Mohamad-Ali; Davy, Alice

doi:10.1101/2020.06.29.177469

Cited by 2 publications

(4 citation statements)

References 54 publications

(51 reference statements)

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“…Modern genetic approaches investigating potential cell cycle re-entry in vertebrate brains began taking shape in the early 2000’s. In recent years, observations of bona fide polyploidy in neurons of the retinal ganglion of the chicken and mouse, cerebral cortex of the rat and neocortex of the mouse have been made using modern flow cytometry and high resolution imaging techniques ( Morillo et al, 2010 ; López-Sánchez and Frade, 2013 ; Ovejero-Benito and Frade, 2015 ; Martin et al, 2017 ; Jungas et al, 2020 ). Work from the Frade lab has shown that the neurons of the retinal ganglion become tetraploid in an E2F-dependent manner.…”

Section: Are All Terminally Differentiated Neurons Permanently Diploid and In G0?mentioning

confidence: 99%

“…However, this endoreplication program is differentially regulated in chick and mouse central nervous system, as p27 kip1 is necessary for tetraploidization in the chick, but not the mouse RGCs ( López-Sánchez and Frade, 2013 ; Ovejero-Benito and Frade, 2013 , 2015 ). Further advances in imaging and flow cytometry techniques have identified polyploid pyramidal neurons in the cerebrum of the rat, and the neocortex of the mouse, but the function and underlying cause for their polyploidy remain elusive ( Sigl-Glöckner and Brecht, 2017 ; Jungas et al, 2020 ). These studies show sufficient evidence that polyploidization does indeed occur in higher vertebrates, suggesting that neuronal polyploidization may be a well conserved phenomenon.…”

Section: Are All Terminally Differentiated Neurons Permanently Diploid and In G0?mentioning

confidence: 99%

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Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration

Nandakumar

Rozich

Buttitta

2021

Front. Cell Dev. Biol.

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Terminally differentiated cells of the nervous system have long been considered to be in a stable non-cycling state and are often considered to be permanently in G0. Exit from the cell cycle during development is often coincident with the differentiation of neurons, and is critical for neuronal function. But what happens in long lived postmitotic tissues that accumulate cell damage or suffer cell loss during aging? In other contexts, cells that are normally non-dividing or postmitotic can or re-enter the cell cycle and begin replicating their DNA to facilitate cellular growth in response to cell loss. This leads to a state called polyploidy, where cells contain multiple copies of the genome. A growing body of literature from several vertebrate and invertebrate model organisms has shown that polyploidy in the nervous system may be more common than previously appreciated and occurs under normal physiological conditions. Moreover, it has been found that neuronal polyploidization can play a protective role when cells are challenged with DNA damage or oxidative stress. By contrast, work over the last two and a half decades has discovered a link between cell-cycle reentry in neurons and several neurodegenerative conditions. In this context, neuronal cell cycle re-entry is widely considered to be aberrant and deleterious to neuronal health. In this review, we highlight historical and emerging reports of polyploidy in the nervous systems of various vertebrate and invertebrate organisms. We discuss the potential functions of polyploidization in the nervous system, particularly in the context of long-lived cells and age-associated polyploidization. Finally, we attempt to reconcile the seemingly disparate associations of neuronal polyploidy with both neurodegeneration and neuroprotection.

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Section: Are All Terminally Differentiated Neurons Permanently Diploid and In G0?mentioning

confidence: 99%

Section: Are All Terminally Differentiated Neurons Permanently Diploid and In G0?mentioning

confidence: 99%

Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration

Nandakumar

Rozich

Buttitta

2021

Front. Cell Dev. Biol.

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“…To consolidate these data, we also quantified the total number of PAX6+ and TBR2+ cells in Control (Ctl) and CDC25B cKO cortices using cytometry (Jungas et al 2020). While the total number of PAX6+ cells is not modified, the number of TBR2+ cells is significantly reduced in CDC25B cKO at E14.5 confirming that bIP but not aRGs production is affected in CDC25B cKO (Figure 3-figure supplement 1) .…”

Section: Resultsmentioning

confidence: 99%

“…Flow cytometry analysis were conducted as described in (Jungas et al 2020). Cortical hemispheres were collected in PBS-1% FCS and cells mechanically dissociated through a 40-μm nylon mesh (Clearline).…”

Section: Methodsmentioning

confidence: 99%

Control of G2 phase duration by CDC25B modulates the switch from direct to indirect neurogenesis in the neocortex

Roussat

Jungas

Audouard

et al. 2021

Preprint

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During development, cortical neurons are produced in a temporally regulated sequence from apical progenitors, directly, or indirectly through the production of intermediate basal progenitors. The balance between these major progenitors types is determinant for the production of the proper number and types of neurons and it is thus important to decipher the cellular and molecular cues controlling this equilibrium. Here we address the role of a cell cycle regulator, the CDC25B phosphatase, in this process. We show that deleting CDC25B in apical progenitors leads to a transient increase of the production of TBR1+ neurons at the expense of TBR2+ basal progenitors in mouse neocortex. This phenotype is associated with lengthening of the G2 phase of the cell cycle, the total cell cycle length being unaffected. Using in utero electroporation and cortical slice cultures, we demonstrate that the defect in TBR2+ basal progenitor production requires interaction with CDK1 and is due to the G2 phase lengthening in CDC25B mutants. Altogether, this study identifies a new role for CDC25B and the length of the G2 phase in direct versus indirect neurogenesis at early stages of the cortical development.

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Population Dynamics and Neuronal Polyploidy in the Developing Neocortex

Cited by 2 publications

References 54 publications

Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration

Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration

Control of G2 phase duration by CDC25B modulates the switch from direct to indirect neurogenesis in the neocortex

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