Ephrin-B2/EphA4 forward signaling is required for regulation of radial migration of cortical neurons in the mouse

Abstract

Postmitotic neurons in the neocortex migrate to appropriate positions and form layered structures of nascent cortex during brain development. The migration of these neurons requires precise control and coordination of a large number of molecules such as axon guidance cues. The Eph-ephrin signaling pathway plays important roles in the development of the nervous system in a wide variety of ways, including cell segregation, axon pathfinding, and neuron migration. However, the role of ephrin-B2/EphA4 signaling in cortical neuron migration remains elusive. Here we demonstrated that ephrin-B2 and its receptor EphA4 were expressed in complementary and overlapping patterns in the developing neocortex. Deletion of the EphA4 gene in the embryonic cerebral cortex resulted in faster migration of cortical neurons, whereas knockdown or overexpression of ephrin-B2 did not alter the normal process of migration. These results suggest that ephrin-B2 forward signaling through EphA4 is required for the precise control of cortical neuron migration.

Replicating infant astrocyte behavior in the adult after brain injury improves outcomes

“…However, our data suggests that ephrin-A1 signaling disrupts ephrin-A5/ EphA2 (ephrin-A1's cognate receptor) [58] and EphA4 (high-affinity receptor) [41] -dependent astrocyte reactivity. This is consistent with the known roles of EphA2 and EphA4 as modulators of cell migration [59][60][61], cell-cycle [25,62,63] and astrocyte reactivity [10,23,25]. Specifically, the involvement of ephrin-A5/ EphA4 signaling on reactive astrocytes, which promotes proliferation and motility, via the mitogen-activated protein kinase (MAPK) and Rho-dependent pathways [25,64,65].…”

Foxg1 Regulates the Postnatal Development of Cortical Interneurons

“…Brains were harvested as described above, with that phosphate buffered saline and 30% sucrose were prepared using diethylpyrocarbonate (DEPC)-treated water. In situ hybridization was performed as previously described (Zhao et al 2006;Hu et al 2014). The information of SST, NPY, and VIP probes is listed in Table 1.…”

Direct interaction of receptor tyrosine kinases, EphA4 and PDGFRβ, plays an important role in the proliferation of neural stem cells

“…Cell-cell contact-dependent signaling pathway from ephrins to Ephs (forward signaling) or from Ephs to ephrins (reverse signaling) regulates many physiological and developmental processes. Bidirectional signaling possesses many functions, including neural stem cell maintenance and plasticity regulation in the proliferation zone of adult brain, 6,7 neuron migration, 8 axon guidance, 9 angiogenesis, 10 bone homeostasis, 11 embryonic patterning, 12 tumorgenesis, [13][14][15][16][17][18] insulin secretion, 19 and so on. EphA4 expression is very high in the brain, and recently, EphA4 has been proposed to be implicated in Alzheimer's disease (AD), 20,21 Parkinson's disease (PD), 22,23 amyotrophic lateral sclerosis (ALS), 24 and other neurodegenerative diseases.…”