Mechanisms of progenitor maturation are conserved in the striatum and cortex.
We recently reported that developmental changes in the expression of epidermal growth factor receptors (EGFRs) by cortical progenitor cells regulate their fate and migration. Higher levels of EGFRs are expressed by later embryonic progenitor cells and are required for several responses to EGF family ligands, including astrocyte differentiation and migration. Progenitor cells in the ganglionic eminence (GE), the forerunner of the striatum, also exhibit a developmental increase in EGFR expression. The striatum differs from the cortex in several respects, including cytoarchitecture, the timing of changes in EGFRs, and the level of transforming growth factor-alpha (TGFalpha) expression. To determine whether signaling mediated by EGFRs in GE progenitors regulates their fate and migration as observed in cortex, we used a retrovirus to increase EGFR expression in embryonic GE progenitor cells prematurely. As in cortex, premature elevation of EGFRs promoted the departure of GE progenitors from the ventricular zone and their differentiation into astrocytes. Settling patterns of infected cells in the striatum, however, differed from the patterns observed in cortex. In addition, the extent of premature astrocyte differentiation reached similar levels in striatal cells, even in the presence of greater endogenous TGFalpha. These findings suggest that additional factors play an important role in modulating EGFR-mediated changes in cell fate. Together with previous studies in cortex, these observations in the striatum indicate that a conserved mechanism involving developmental changes in EGFR expression regulates cell fate and the timing of migration.
Burrows
R C
RC
Department of Radiology, University of Washington, Seattle, Wash., USA.
Lillien
L
L
Levitt
P
P
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D002552:Cerebral Ventricles / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology*; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012190:Retroviridae / Q000235:genetics; D012192:Retroviridae Infections / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D066246:ErbB Receptors