Astroglial PTEN loss disrupts neuronal lamination by dysregulating radial glia-guided neuronal migration

Yi Wen, Wenjun Li, Gourav Roy Choudhury, Runlian He, Tiger Yang, Ran Liu, Kunlin Jin, Shaohua Yang

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

PTEN plays an important role not only in tumorigenesis but also in the normal development of central nervous system. PTEN loss in neural progenitor cells during embryogenesis disrupts migration and proper formation of the brain laminar structure. We generated a conditional PTEN knockout mouse by crossing mice that express Cre recombinase driven by the human GFAP promoter to a floxed PTEN gene to investigate the role of astroglial PTEN signaling pathway in neuronal patterning and lamination. We found PTEN loss not only in astroglial cells, but also in radial glia-derived neurons in hGFAP-Cre+/-/PTENloxp/loxp transgenic mice. Homozygous hGFAP-Cre+/-/PTENloxp/loxp transgenic mice showed progressive brain enlargement with cellular disorganization that occurred predominantly in hippocampus and cerebellum and died by postnatal day 20. Confocal images show that nestin-positive radial glial cells were observed in the hippocampus, cortex, and cerebellum at postnatal day 0 in homozygous hGFAP-Cre+/-/PTENloxp/loxp, but not in heterozygous hGFAP-Cre+/-/PTENloxp/- and hGFAP-Cre-/-/PTENloxp/loxp mice. Homozygous hGFAP-Cre+/-/PTENloxp/loxp transgenic mouse eyes, which lack radial glial lineage, were able to develop normal architectonics after birth. In addition, we also found that neuronal progenitor migration was defected at postnatal day 0 in homozygous hGFAP-Cre+/-/PTENloxp/loxp mice. These results suggest that PTEN has a critical role in regulating radial glial differentiation, proliferation, maturation, and eventually neuronal patterning in central nervous system in a spatio-temporal dependent manner.

Original languageEnglish
Pages (from-to)113-126
Number of pages14
JournalAging and Disease
Volume4
Issue number3
StatePublished - 1 Jan 2013

Fingerprint

Neuroglia
Transgenic Mice
Cerebellum
Hippocampus
Central Nervous System
Ependymoglial Cells
Nestin
Brain
Knockout Mice
Embryonic Development
Carcinogenesis
Stem Cells
Parturition
Neurons
Genes
Cre recombinase

Keywords

  • Neurogenesis
  • Neuronal lamination
  • PTEN
  • Radial glia

Cite this

Wen, Yi ; Li, Wenjun ; Choudhury, Gourav Roy ; He, Runlian ; Yang, Tiger ; Liu, Ran ; Jin, Kunlin ; Yang, Shaohua. / Astroglial PTEN loss disrupts neuronal lamination by dysregulating radial glia-guided neuronal migration. In: Aging and Disease. 2013 ; Vol. 4, No. 3. pp. 113-126.
@article{1ef8220753d24f19aea454c4dad81f0a,
title = "Astroglial PTEN loss disrupts neuronal lamination by dysregulating radial glia-guided neuronal migration",
abstract = "PTEN plays an important role not only in tumorigenesis but also in the normal development of central nervous system. PTEN loss in neural progenitor cells during embryogenesis disrupts migration and proper formation of the brain laminar structure. We generated a conditional PTEN knockout mouse by crossing mice that express Cre recombinase driven by the human GFAP promoter to a floxed PTEN gene to investigate the role of astroglial PTEN signaling pathway in neuronal patterning and lamination. We found PTEN loss not only in astroglial cells, but also in radial glia-derived neurons in hGFAP-Cre+/-/PTENloxp/loxp transgenic mice. Homozygous hGFAP-Cre+/-/PTENloxp/loxp transgenic mice showed progressive brain enlargement with cellular disorganization that occurred predominantly in hippocampus and cerebellum and died by postnatal day 20. Confocal images show that nestin-positive radial glial cells were observed in the hippocampus, cortex, and cerebellum at postnatal day 0 in homozygous hGFAP-Cre+/-/PTENloxp/loxp, but not in heterozygous hGFAP-Cre+/-/PTENloxp/- and hGFAP-Cre-/-/PTENloxp/loxp mice. Homozygous hGFAP-Cre+/-/PTENloxp/loxp transgenic mouse eyes, which lack radial glial lineage, were able to develop normal architectonics after birth. In addition, we also found that neuronal progenitor migration was defected at postnatal day 0 in homozygous hGFAP-Cre+/-/PTENloxp/loxp mice. These results suggest that PTEN has a critical role in regulating radial glial differentiation, proliferation, maturation, and eventually neuronal patterning in central nervous system in a spatio-temporal dependent manner.",
keywords = "Neurogenesis, Neuronal lamination, PTEN, Radial glia",
author = "Yi Wen and Wenjun Li and Choudhury, {Gourav Roy} and Runlian He and Tiger Yang and Ran Liu and Kunlin Jin and Shaohua Yang",
year = "2013",
month = "1",
day = "1",
language = "English",
volume = "4",
pages = "113--126",
journal = "Aging and Disease",
issn = "2152-5250",
publisher = "International Society on Aging and Disease",
number = "3",

}

Astroglial PTEN loss disrupts neuronal lamination by dysregulating radial glia-guided neuronal migration. / Wen, Yi; Li, Wenjun; Choudhury, Gourav Roy; He, Runlian; Yang, Tiger; Liu, Ran; Jin, Kunlin; Yang, Shaohua.

In: Aging and Disease, Vol. 4, No. 3, 01.01.2013, p. 113-126.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Astroglial PTEN loss disrupts neuronal lamination by dysregulating radial glia-guided neuronal migration

AU - Wen, Yi

AU - Li, Wenjun

AU - Choudhury, Gourav Roy

AU - He, Runlian

AU - Yang, Tiger

AU - Liu, Ran

AU - Jin, Kunlin

AU - Yang, Shaohua

PY - 2013/1/1

Y1 - 2013/1/1

N2 - PTEN plays an important role not only in tumorigenesis but also in the normal development of central nervous system. PTEN loss in neural progenitor cells during embryogenesis disrupts migration and proper formation of the brain laminar structure. We generated a conditional PTEN knockout mouse by crossing mice that express Cre recombinase driven by the human GFAP promoter to a floxed PTEN gene to investigate the role of astroglial PTEN signaling pathway in neuronal patterning and lamination. We found PTEN loss not only in astroglial cells, but also in radial glia-derived neurons in hGFAP-Cre+/-/PTENloxp/loxp transgenic mice. Homozygous hGFAP-Cre+/-/PTENloxp/loxp transgenic mice showed progressive brain enlargement with cellular disorganization that occurred predominantly in hippocampus and cerebellum and died by postnatal day 20. Confocal images show that nestin-positive radial glial cells were observed in the hippocampus, cortex, and cerebellum at postnatal day 0 in homozygous hGFAP-Cre+/-/PTENloxp/loxp, but not in heterozygous hGFAP-Cre+/-/PTENloxp/- and hGFAP-Cre-/-/PTENloxp/loxp mice. Homozygous hGFAP-Cre+/-/PTENloxp/loxp transgenic mouse eyes, which lack radial glial lineage, were able to develop normal architectonics after birth. In addition, we also found that neuronal progenitor migration was defected at postnatal day 0 in homozygous hGFAP-Cre+/-/PTENloxp/loxp mice. These results suggest that PTEN has a critical role in regulating radial glial differentiation, proliferation, maturation, and eventually neuronal patterning in central nervous system in a spatio-temporal dependent manner.

AB - PTEN plays an important role not only in tumorigenesis but also in the normal development of central nervous system. PTEN loss in neural progenitor cells during embryogenesis disrupts migration and proper formation of the brain laminar structure. We generated a conditional PTEN knockout mouse by crossing mice that express Cre recombinase driven by the human GFAP promoter to a floxed PTEN gene to investigate the role of astroglial PTEN signaling pathway in neuronal patterning and lamination. We found PTEN loss not only in astroglial cells, but also in radial glia-derived neurons in hGFAP-Cre+/-/PTENloxp/loxp transgenic mice. Homozygous hGFAP-Cre+/-/PTENloxp/loxp transgenic mice showed progressive brain enlargement with cellular disorganization that occurred predominantly in hippocampus and cerebellum and died by postnatal day 20. Confocal images show that nestin-positive radial glial cells were observed in the hippocampus, cortex, and cerebellum at postnatal day 0 in homozygous hGFAP-Cre+/-/PTENloxp/loxp, but not in heterozygous hGFAP-Cre+/-/PTENloxp/- and hGFAP-Cre-/-/PTENloxp/loxp mice. Homozygous hGFAP-Cre+/-/PTENloxp/loxp transgenic mouse eyes, which lack radial glial lineage, were able to develop normal architectonics after birth. In addition, we also found that neuronal progenitor migration was defected at postnatal day 0 in homozygous hGFAP-Cre+/-/PTENloxp/loxp mice. These results suggest that PTEN has a critical role in regulating radial glial differentiation, proliferation, maturation, and eventually neuronal patterning in central nervous system in a spatio-temporal dependent manner.

KW - Neurogenesis

KW - Neuronal lamination

KW - PTEN

KW - Radial glia

UR - http://www.scopus.com/inward/record.url?scp=84901291380&partnerID=8YFLogxK

M3 - Article

VL - 4

SP - 113

EP - 126

JO - Aging and Disease

JF - Aging and Disease

SN - 2152-5250

IS - 3

ER -