ORIGINAL RESEARCH article

Front. Cell Dev. Biol.

Sec. Stem Cell Research

Volume 13 - 2025 | doi: 10.3389/fcell.2025.1612177

This article is part of the Research TopicNeurodevelopment: From Stem Cells to Signaling and BeyondView all 5 articles

Rnd3 deletion affects neuroblast behavior through the RhoA/ROCK pathway but not neural stem cells in postnatal mice subventricular zone

Provisionally accepted
Amalia  Solana OrtsAmalia Solana Orts1Germán  BelenguerGermán Belenguer2Begoña  Ballester LurbeBegoña Ballester Lurbe1Olga  Gómez RodaOlga Gómez Roda3Ignacio  Perez-RogerIgnacio Perez-Roger1José  Terrado VicenteJosé Terrado Vicente3Enric  Poch JiménezEnric Poch Jiménez1*Alexandra  BizyAlexandra Bizy1*
  • 1Department of Biomedical Sciences, School of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, Spain
  • 2Departamento de Biología Celular, Biología Funcional y Antropología Física, Universidad de Valencia, Valencia, Spain
  • 3Department of Animal Medicine and Surgery, Faculty of Veterinary Science, CEU Cardenal Herrera University, Alfara del Patriarca, Spain

The final, formatted version of the article will be published soon.

In the subventricular zone (SVZ), neural stem cells (NSCs) generate neural progenitor cells (NPCs), which proliferate and differentiate into neuroblasts (NBs) that will travel along the rostral migratory stream (RMS) to the olfactory bulbs (OBs), where they mature into interneurons. Rnd3, a member of the Rho GTPase family, regulates cytoskeletal dynamics, neuronal morphology, and survival, primarily by interacting with the RhoA/ROCK pathway. In the central nervous system, Rnd3 is highly expressed during early postnatal development and is essential for neural function, axonal myelination, and neuronal polarization, as its deficiency leads to severe motor and neurodevelopmental impairments. In this study we show that NBs from Rnd3 KO mice accumulate in the SVZ and that these are principally characterized as late/migrating NBs. We investigated whether the observed accumulation results from increased proliferation and/or differentiation potential of NSCs and NPCs, and/or altered NB migration to the OBs through the RMS, potentially accompanied by increased proliferation. Our in vitro experiments indicate that the loss of Rnd3 does not affect NSC behavior. In addition, RNA sequencing reveals that Rnd3 expression is highest in NBs, particularly in late-stage NBs, suggesting a potential role in migration. Furthermore, gene expression analyses indicate that the loss of Rnd3 may disrupt NB cytoskeletal dynamics by altering the expression of key components of the RhoA/ROCK signaling pathway. These findings provide mechanistic insights into how Rnd3 deletion impairs NB migration.

Keywords: subventricular zone (SVZ), Rnd3/ RhoE, Neural stem cell (NSC), neuroblast migration, RhoA/ROCK pathway

Received: 15 Apr 2025; Accepted: 04 Jun 2025.

Copyright: © 2025 Solana Orts, Belenguer, Ballester Lurbe, Gómez Roda, Perez-Roger, Terrado Vicente, Poch Jiménez and Bizy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Enric Poch Jiménez, Department of Biomedical Sciences, School of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, Spain
Alexandra Bizy, Department of Biomedical Sciences, School of Health Sciences, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, Spain

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