Ephrin-B2 Paces Neuronal Production in the Developing Neocortex

Abstract

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>During 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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Here, 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Altogether, our data uncover a role for ephrin-B2 in embryonic neurogenesis and emphasizes the plasticity of neuronal production in the neocortex.</jats:p></jats:sec>

Characterization and manipulation of Corticothalamic neurons in associative cortices using Syt6‐Cre transgenic mice

“…The rabbit polyclonal anti‐TBR1 was raised against amino acids 50–150 of mouse TBR1(Abcam 31940, ). It is a widely used antibody to detect TBR1 in the mouse neocortex (Kischel et al., 2020; Ratie et al., 2020 Woodworth et al., 2016). The pattern of immunostaining we observed was similar to previously published immunostaining of TBR1.…”

Population Dynamics and Neuronal Polyploidy in the Developing Neocortex

“…Indeed, to compare our data to previously published data collected by counting cells on tissue section (2D method), we surveyed 7 previously published studies (Alsiö et al, 2013;Fei et al, 2014;Kischel et al, 2020;Knock et al, 2015;Lanctot et al, 2017;Postel et al, 2019;Wang et al, 2016;Yoon et al, 2017) and collected reported cell numbers at the 7 developmental stages (Sup Table 1). Graphical representation of the data (Sup Figure 3B) shows overall conservation of the profiles for each of the 4 cell populations with some differences, specifically in the number of Tbr2+ progenitors.…”