Ephrin B1 Is Expressed on Neuroepithelial Cells in Correlation with Neocortical Neurogenesis

Abstract

To identify molecules involved in neurogenesis, we have raised monoclonal antibodies against embryonic day 12.5 mouse telencephalon. One antibody, monoclonal antibody 25H11, stains predominantly the ventricular zone of the anterior and lateral telencephalon. Purification of the 25H11 antigen, a 47 kDa integral membrane protein, from Ϸ2500 mouse telencephali reveals its identity with ephrin B1. Ephrin B1 appears at the onset of neocortical neurogenesis, being first expressed in neuron-generating neuroepithelial cells and rapidly thereafter in virtually all neuroepithelial cells. Expression of ephrin B1 persists through the period of neocortical neurogenesis and is downregulated thereafter. Ephrin B1 is present on the ventricular as well as basolateral plasma membrane of neuroepithelial cells and exhibits an ventricular-high to pial-low gradient across the ventricular zone. Expression of ephrin B1 is also detected on radial glial cells, extending all the way to their pial endfeet, and on neurons in the mantle/intermediate zone but not in the cortical plate. Our results suggest that ephrin B1, presumably via ephrin-Eph receptor signaling, has a role in neurogenesis. Given the ventricular-to-pial gradient of ephrin B1 on the neuroepithelial cell surface and its known role in cell migration in other systems mediated by its repulsive properties, we propose that ephrin B1 may be involved in the migration of newborn neurons out from the ventricular zone toward the neocortex.

Ephrin B1 maintains apical adhesion of neural progenitors

“…We and others have shown that this is due to the formation of ectopic Eph-ephrin boundaries within developing tissues of heterozygote individuals (Compagni et al, 2003;Davy et al, 2006). In the developing cortex, ephrin B1 is expressed in APs from the neuroepithelial stage in a ventricularhigh to pial-low gradient (Stuckmann et al, 2001). Ephrin B1 is required to maintain the neural progenitor fate at late stages of cortical development (Murai et al, 2010;Qiu et al, 2008) and we have shown recently that ephrin B1 reverse signaling controls the switch between progenitor maintenance and neuronal differentiation by engaging in a feedback loop involving miR-124, a pro-neuronal miRNA (Arvanitis et al, 2010).…”

“…1G-I), suggesting that the integrity of the neuroepithelium was compromised in the absence of ephrin B1. Because expression of ephrin B1 persists in APs at later stages of cortical development (Stuckmann et al, 2001), we wondered what would be the consequences of Efnb1 loss of function for development of the neocortex. To study the physiological function of ephrin B1 and to avoid phenotypes that could be due to formation of ectopic Eph-ephrin boundaries in Efnb1 +/− embryos, we decided to focus our analysis on Efnb1 −/− embryos.…”

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

“…Finally, delta-like 1 mutant mice show defects in the VZ, with a thinning of the VZ and premature neuronal differentiation (Yun et al, 2002). Ephrins B1 and A5 and Eph A4 and A7 receptors are expressed in the VZ (Mackarehtschian et al, 1999;Stuckmann et al, 2001;Greferath et al, 2002;Depaepe et al, 2005). With its apical to basal expression gradient in the VZ and diminished expression in the cortex, Ephrin B1 is thought to facilitate cell migration outside of the VZ (Stuckmann et al, 2001) while ephrin A5/Eph A7 promotes apoptosis of the stem/precursor population (Depaepe et al, 2005).…”

Concurrent Binding of Anti-EphA3 Antibody and Ephrin-A5 Amplifies EphA3 Signaling and Downstream Responses: Potential as EphA3-Specific Tumor-Targeting Reagents

“…However, most ephrins can bind and activate several Eph receptors within their subclass with comparable affinities (9,10), a redundancy that provides a considerable challenge for selective targeting of Eph-or ephrin-expressing tumor cells with soluble Eph or ephrin proteins. In this regard, monoclonal antibodies can be more specific and have been described for EphA3 (11), EphB2 (12), EphB6 (13), mouse ephrin B1 (14), and EphA2 (15), whereby an apparent antiproliferative activity of the latter (15) has not been reproduced for any of the other antibodies (12). We previously used a monoclonal antibody (mAb), IIIA4, raised against LK63 human acute pre-B leukemia cells to affinity isolate EphA3 (11).…”