Biology subjects

Fawal, M.-A.

Publications and source records attributed to Fawal, M.-A..

3 recordsLinked to original sources

bioRxiv2020

Population dynamics and neuronal polyploidy in the developing neocortex

SUMMARYThe mammalian neocortex is composed of different subtypes of neurons which are generated during embryogenesis by sequential differentiation of neural progenitors. While molecular mechanisms that control neuronal production in the developing neocortex have been extensively studied, the dynamics and absolute numbers of the different progenitor and neuronal populations are still poorly characterized. Here we describe a medium throughput approach based on flow cytometry and well known identity markers of cortical subpopulations to collect quantitative data over the course of mouse neocortex development. We collected a complete dataset in a physiological developmental context on two progenitor and two neuron populations, including relative proportions and absolute numbers. Our study reveals unexpected numbers of progenitors. In addition, we discovered that a fraction of neurons in the developing mouse neocortex are polyploid.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗

bioRxiv2020

Ephrin-B2 paces neuronal production in the developing neocortex

BackgroundDuring mammalian cerebral cortex development, different types of projection neurons are produced in a precise temporal order and in stereotypical numbers. The mechanisms regulating timely generation of neocortex projection neurons and ensuring production in sufficient numbers of each neuronal identity is only partially understood. ResultsHere, we show that ephrin-B2, a member of the Eph:ephrin cell-to-cell communication pathway, sets the neurogenic tempo in the neocortex. Indeed, conditional mutant embryos for ephrin-B2 exhibit a transient delay in neurogenesis and acute stimulation of Eph signaling by in utero injection of synthetic ephrin-B2 led to a transient increase in neuronal production. Using genetic approaches we show that ephrin-B2 acts on neural progenitors to control their differentiation in a juxtacrine manner. Unexpectedly, we observed that perinatal neuron numbers recovered following both loss or gain of ephrin-B2, highlighting the ability of neural progenitors to adapt their behavior to the state of the system in order to produce stereotypical numbers of neurons. ConclusionsAltogether, our data uncover a role for ephrin-B2 in embryonic neurogenesis and emphasizes the plasticity of neuronal production in the neocortex.

developmental biology↗

bioRxiv2017

Crosstalk between one carbon metabolism and eph signaling promotes neural stem cells differentiation through epigenetic remodeling

Metabolic pathways, once seen as a mere consequence of cell states, have emerged as active players in dictating different cellular events such as proliferation, self-renewal and differentiation. Several studies have reported a role for folate-dependent 1-carbon (1C) metabolism in stem cells, however, its exact mode of action and how it interacts with other cues is largely unknown. Here, we report a link between the Eph:ephrin cell-cell communication pathway and 1C metabolism in controlling differentiation of neural stem cells. Transcriptional and functional analyses following ephrin stimulation revealed alterations in folate metabolism-related genes and enzymatic activity. In vitro and in vivo data indicate that Eph-B forward signaling alters the methylation state of H3K4 by regulating 1C metabolism, and locks neural stem cells in a differentiation-ready state. The functional link between cell-cell communication, metabolism and epigenetic remodeling identifies a novel triad in the control of stem cell self-renewal vs. differentiation.\n\nHIGHLIGHTSO_LI1C folate metabolism is regulated by local cell-to-cell communication\nC_LIO_LIDescription of Eph-B transcriptional response in NSC\nC_LIO_LIEph activation decreases the expression and activity of DHFR\nC_LIO_LIInhibition of DHFR modifies epigenetic marks and impairs self-renewal of neural stem cells\nC_LIO_LIDecreased H3K4 methylation locks neural stem cells in a pro-differentiation state\nC_LI\n\neTOC BLURBFawal et al. present evidence that Eph-B forward signaling inhibits 1C folate metabolism in neural stem cells leading to alteration of H3K4 methylation on key progenitor genes. In addition, they show that these epigenetic changes are inherited and maintained in the long term, thus locking NSC into a differentiation ready state.

developmental biology↗