EGFRs mediate chemotactic migration in the developing telencephalon.
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 TGFalpha. 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.
Caric
D
D
Department of Neurobiology and Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, W1454 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Raphael
H
H
Viti
J
J
Feathers
A
A
Wancio
D
D
Lillien
L
L
D000818:Animals; D002633:Chemotaxis / Q000502:physiology*; D004627:Embryonic Induction; D004815:Epidermal Growth Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013687:Telencephalon / Q000196:embryology* / Q000378:metabolism / Q000637:transplantation; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D019737:Transplants
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors