EGFRs mediate chemotactic migration in the developing telencephalon

Abstract

Epidermal growth factor receptors (EGFRs) have been implicated in the control of migration in the telencephalon, but the mechanism underlying their contribution is unclear. We show that expression of a threshold level of EGFRs confers chemotactic competence in stem cells, neurons and astrocytes in cortical explants. This level of receptor expression is normally achieved by a subpopulation of cells during mid-embryonic development. Cells that express high levels of EGFR are located in migration pathways, including the tangential pathway to the olfactory bulb via the rostral migratory stream (RMS), the lateral cortical stream (LCS) leading to ventrolateral cortex and the radial pathway from proliferative zones to cortical plate. The targets of these pathways express the ligands HB-EGF and/or TGFα. To test the idea that EGFRs mediate chemotactic migration these pathways, we increased the size of the population of cells expressing threshold levels of EGFRs in vivo by viral transduction. Our results suggest that EGFRs mediate migration radially to the cortical plate and ventrolaterally in the LCS, but not tangentially in the RMS. Within the bulb, however, EGFRs also mediate radial migration. Our findings suggest that developmental changes in EGFR expression, together with changes in ligand expression regulate the migration of specific populations of cells in the telencephalon by a chemoattractive mechanism.

Differential Regulation of Telencephalic Pallial–Subpallial Boundary Patterning by Pax6 and Gsh2

“…The LCS populates the basal telencephalic limbic system, in particular the piriform and olfactory cortices and the amygdala (Hirata et al 2002;Carney et al 2006, Bai et al 2008. The PSB also seeds the embryonic and postnatal SVZ stem cell niche and their subsequent progeny that migrate along the RMS to generate diverse subtypes of OB interneurons (Waclaw et al 2006;Kohwi et al 2007) Our analysis of EGFR expression, a previously identified marker of LCS migratory cells (Caric et al 2001), reveals that both the subpallial (Dlx2+) and pallial (Pax6+) subpopulations are both EGFR+. As Tgfa, a known ligand for EGFR, is expressed in the VP, it is possible that this signaling pathway is required for specification/migration of EGFR+ cells of the LCS.…”

“…Alterations in LCS cell migration in Gsh2, Sey, and Sey/ Gsh2 double mutants at E15.5 To examine defects in cell migration along the LCS in Gsh2, Sey, and Sey/Gsh2 double mutant mice, we carried out immunohistochemical analysis for EGFR, which is expressed at the PSB and in migrating cells of the LCS (Caric et al 2001). First, we further characterized the cell types of the PSB that express EGFR.…”

Single‐cell analysis reveals dynamic changes of neural cells in developing human spinal cord

“…EGFR is essential for growth and differentiation in various developing systems, including the nervous system (Caric et al , 2001; Xian & Zhou, 2004; Chen et al , 2016; Romano & Bucci, 2020). Here, we found that EGFR‐expressing transitional glial cells were present and exhibited a radial morphology at the onset of gliogenesis.…”

Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

“…EGFR signaling generally regulates cell proliferation, growth, differentiation and cell survival ( Oda et al, 2005 ). In the developing brain, the EGFR is increasingly expressed over time ( Romano and Bucci, 2020 ) and is mainly found in proliferating and migratory brain regions ( Kornblum et al, 1997 ; Caric et al, 2001 ). The EGFR is therefore indispensable for proper rodent brain development ( Romano and Bucci, 2020 ).…”