Hoelzl-Wenig, G. | bioRxiv Science

bioRxiv2025

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

neuroscience↗

bioRxiv2020

Basal Neural Stem Cells in the Subventricular Zone Drive Postnatal Neurogenesis with Apical Stem Cells Acting as Proliferation Gatekeepers

According to the current consensus, neural stem cells (NSCs) apically contacting the lateral ventricle generate differentiated progenitors by rare asymmetric divisions or by relocating to the basal side of the ventricular-subventricular zone V-SVZ. Both processes will then ultimately lead to the generation of adult-born olfactory bulb (OB) interneurons. In contrast to this view, we here found that adult-born OB interneurons largely derive from an additional NSC type resident in the basal V-SVZ. Despite being both capable of self-renewal and long-term quiescence, apical and basal NSCs differ in Nestin expression, primary cilia extension and frequency of cell division. The expression of Notch-related genes also differed between the two NSC groups and Notch-activation was greatest in apical NSCs. Apical downregulation of Notch-effector Hes1 decreased Notch activation while increasing proliferation across the niche and neurogenesis from apical NSCs. Underscoring their different roles in neurogenesis, lactation-dependent increase in neurogenesis was paralleled by extra activation of basal but not apical NSCs. Thus, basal NSCs support OB neurogenesis whereas apical NSCs impart Notch-mediated lateral inhibition across the V-SVZ.

cell biology↗