Retinoic acid regulates postnatal neurogenesis in the murine subventricular zone-olfactory bulb pathway

Tsu Wei Wang, Helen Zhang, Jack M. Parent

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Neurogenesis persists throughout life in the rodent subventricular zone (SVZ)-olfactory bulb pathway. The molecular regulation of this neurogenic circuit is poorly understood. Because the components for retinoid signaling are present in this pathway, we examined the influence of retinoic acid (RA) on postnatal SVZ-olfactory bulb neurogenesis. Using both SVZ neurosphere stem cell and parasagittal brain slice cultures derived from postnatal mouse, we found that RA exposure increased neurogenesis by enhancing the proliferation and neuronal differentiation of forebrain SVZ neuroblasts. The RA precursor retinol had a similar effect, which was reversed by treating cultures with the RA synthesis inhibitor disulfiram. Electroporation of dominant-negative retinoid receptors into the SVZ of slice cultures also blocked neuroblast migration to the olfactory bulb and altered the morphology of the progenitors. Moreover, the administration of disulfiram to neonatal mice decreased in vivo cell proliferation in the striatal SVZ. These results indicate that RA is a potent mitogen for SVZ neuroblasts and is required for their migration to the olfactory bulb. The regulation of multiple steps in the SVZ-olfactory bulb neurogenic pathway by RA suggests that manipulation of retinoid signaling is a potential therapeutic strategy to augment neurogenesis after brain injury.

Original languageEnglish
Pages (from-to)2721-2732
Number of pages12
JournalDevelopment
Volume132
Issue number12
DOIs
Publication statusPublished - 2005 Jun 1

Fingerprint

Olfactory Pathways
Lateral Ventricles
Olfactory Bulb
Neurogenesis
Tretinoin
Retinoids
Disulfiram
Corpus Striatum
Electroporation
Prosencephalon
Vitamin A
Mitogens
Brain Injuries
Rodentia
Stem Cells
Cell Proliferation
Brain

Keywords

  • Neural stem cell
  • Neuronal migration
  • Retinoid signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Retinoic acid regulates postnatal neurogenesis in the murine subventricular zone-olfactory bulb pathway. / Wang, Tsu Wei; Zhang, Helen; Parent, Jack M.

In: Development, Vol. 132, No. 12, 01.06.2005, p. 2721-2732.

Research output: Contribution to journalArticle

@article{a3f5083575444e1ea190cbdbec24cda9,
title = "Retinoic acid regulates postnatal neurogenesis in the murine subventricular zone-olfactory bulb pathway",
abstract = "Neurogenesis persists throughout life in the rodent subventricular zone (SVZ)-olfactory bulb pathway. The molecular regulation of this neurogenic circuit is poorly understood. Because the components for retinoid signaling are present in this pathway, we examined the influence of retinoic acid (RA) on postnatal SVZ-olfactory bulb neurogenesis. Using both SVZ neurosphere stem cell and parasagittal brain slice cultures derived from postnatal mouse, we found that RA exposure increased neurogenesis by enhancing the proliferation and neuronal differentiation of forebrain SVZ neuroblasts. The RA precursor retinol had a similar effect, which was reversed by treating cultures with the RA synthesis inhibitor disulfiram. Electroporation of dominant-negative retinoid receptors into the SVZ of slice cultures also blocked neuroblast migration to the olfactory bulb and altered the morphology of the progenitors. Moreover, the administration of disulfiram to neonatal mice decreased in vivo cell proliferation in the striatal SVZ. These results indicate that RA is a potent mitogen for SVZ neuroblasts and is required for their migration to the olfactory bulb. The regulation of multiple steps in the SVZ-olfactory bulb neurogenic pathway by RA suggests that manipulation of retinoid signaling is a potential therapeutic strategy to augment neurogenesis after brain injury.",
keywords = "Neural stem cell, Neuronal migration, Retinoid signaling",
author = "Wang, {Tsu Wei} and Helen Zhang and Parent, {Jack M.}",
year = "2005",
month = "6",
day = "1",
doi = "10.1242/dev.01867",
language = "English",
volume = "132",
pages = "2721--2732",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "12",

}

TY - JOUR

T1 - Retinoic acid regulates postnatal neurogenesis in the murine subventricular zone-olfactory bulb pathway

AU - Wang, Tsu Wei

AU - Zhang, Helen

AU - Parent, Jack M.

PY - 2005/6/1

Y1 - 2005/6/1

N2 - Neurogenesis persists throughout life in the rodent subventricular zone (SVZ)-olfactory bulb pathway. The molecular regulation of this neurogenic circuit is poorly understood. Because the components for retinoid signaling are present in this pathway, we examined the influence of retinoic acid (RA) on postnatal SVZ-olfactory bulb neurogenesis. Using both SVZ neurosphere stem cell and parasagittal brain slice cultures derived from postnatal mouse, we found that RA exposure increased neurogenesis by enhancing the proliferation and neuronal differentiation of forebrain SVZ neuroblasts. The RA precursor retinol had a similar effect, which was reversed by treating cultures with the RA synthesis inhibitor disulfiram. Electroporation of dominant-negative retinoid receptors into the SVZ of slice cultures also blocked neuroblast migration to the olfactory bulb and altered the morphology of the progenitors. Moreover, the administration of disulfiram to neonatal mice decreased in vivo cell proliferation in the striatal SVZ. These results indicate that RA is a potent mitogen for SVZ neuroblasts and is required for their migration to the olfactory bulb. The regulation of multiple steps in the SVZ-olfactory bulb neurogenic pathway by RA suggests that manipulation of retinoid signaling is a potential therapeutic strategy to augment neurogenesis after brain injury.

AB - Neurogenesis persists throughout life in the rodent subventricular zone (SVZ)-olfactory bulb pathway. The molecular regulation of this neurogenic circuit is poorly understood. Because the components for retinoid signaling are present in this pathway, we examined the influence of retinoic acid (RA) on postnatal SVZ-olfactory bulb neurogenesis. Using both SVZ neurosphere stem cell and parasagittal brain slice cultures derived from postnatal mouse, we found that RA exposure increased neurogenesis by enhancing the proliferation and neuronal differentiation of forebrain SVZ neuroblasts. The RA precursor retinol had a similar effect, which was reversed by treating cultures with the RA synthesis inhibitor disulfiram. Electroporation of dominant-negative retinoid receptors into the SVZ of slice cultures also blocked neuroblast migration to the olfactory bulb and altered the morphology of the progenitors. Moreover, the administration of disulfiram to neonatal mice decreased in vivo cell proliferation in the striatal SVZ. These results indicate that RA is a potent mitogen for SVZ neuroblasts and is required for their migration to the olfactory bulb. The regulation of multiple steps in the SVZ-olfactory bulb neurogenic pathway by RA suggests that manipulation of retinoid signaling is a potential therapeutic strategy to augment neurogenesis after brain injury.

KW - Neural stem cell

KW - Neuronal migration

KW - Retinoid signaling

UR - http://www.scopus.com/inward/record.url?scp=21644465569&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21644465569&partnerID=8YFLogxK

U2 - 10.1242/dev.01867

DO - 10.1242/dev.01867

M3 - Article

C2 - 15901659

AN - SCOPUS:21644465569

VL - 132

SP - 2721

EP - 2732

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 12

ER -