Postnatal increase in MRTF-dependent transcription reduces EGFR activation and proliferation of apical but not basal NSCs

In the ventricular-subventricular zone (V-SVZ), both apical and basal NSCs undergo quiescence and proliferation. The epidermal growth factor receptor (EGFR) and interactions with the extracellular matrix are key regulators of adult NSC proliferation and quiescence, respectively. Here, we show that activation of EGFR significantly declines after the first postnatal weeks in apical NSCs. This decline is accompanied by a shift in serum responsive factor (SRF)-dependent transcription in apical NSCs. Specifically, growth-promoting genes targeted by SRF and ternary complex transcription factors are downregulated, whereas those targeted by SRF and myocardin-related transcription factors (MRTFs), including those involved in the extracellular matrix remodeling, are upregulated. Blocking of MRTFs, whose activity is regulated by the Rho/actin pathway and extracellular matrix interactions, restores EGFR activation and EGFR-dependent proliferation in adult apical NSCs. Thus, transcriptional programs regulated by extracellular cues differentially control EGFR activation and proliferation in neonatal and adult apical NSCs. Graphical abstractGraphical representation of the postnatal changes in transcriptional programs observed in apical and basal NSCs in V-SVZ. O_FIG O_LINKSMALLFIG WIDTH=164 HEIGHT=200 SRC="FIGDIR/small/693930v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@ff3367org.highwire.dtl.DTLVardef@87d18eorg.highwire.dtl.DTLVardef@cec1e7org.highwire.dtl.DTLVardef@1c5030_HPS_FORMAT_FIGEXP M_FIG C_FIG