Brain factor-1 controls the proliferation and differentiation of neocortical progenitor cells through independent mechanisms

Carina Hanashima, Lijian Shen, Suzanne C. Li, Eseng Lai

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1NHAA. The BF1NHAA protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1 NHAA protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.

Original languageEnglish
Pages (from-to)6526-6536
Number of pages11
JournalJournal of Neuroscience
Volume22
Issue number15
Publication statusPublished - 2002 Aug 1
Externally publishedYes

Fingerprint

Stem Cells
Brain
Telencephalon
Neocortex
Cell Differentiation
Cell Proliferation
Proteins
DNA
Cerebrum
Basal Ganglia
Morphogenesis
Cell Cycle
Neurons

Keywords

  • BF1
  • Brain development
  • Foxg1
  • Neocortex
  • Neurogenesis
  • Telencephalon
  • Winged helix

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Brain factor-1 controls the proliferation and differentiation of neocortical progenitor cells through independent mechanisms. / Hanashima, Carina; Shen, Lijian; Li, Suzanne C.; Lai, Eseng.

In: Journal of Neuroscience, Vol. 22, No. 15, 01.08.2002, p. 6526-6536.

Research output: Contribution to journalArticle

@article{9c7a619a753a4f8387a4d605e973824e,
title = "Brain factor-1 controls the proliferation and differentiation of neocortical progenitor cells through independent mechanisms",
abstract = "The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1NHAA. The BF1NHAA protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1 NHAA protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.",
keywords = "BF1, Brain development, Foxg1, Neocortex, Neurogenesis, Telencephalon, Winged helix",
author = "Carina Hanashima and Lijian Shen and Li, {Suzanne C.} and Eseng Lai",
year = "2002",
month = "8",
day = "1",
language = "English",
volume = "22",
pages = "6526--6536",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "15",

}

TY - JOUR

T1 - Brain factor-1 controls the proliferation and differentiation of neocortical progenitor cells through independent mechanisms

AU - Hanashima, Carina

AU - Shen, Lijian

AU - Li, Suzanne C.

AU - Lai, Eseng

PY - 2002/8/1

Y1 - 2002/8/1

N2 - The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1NHAA. The BF1NHAA protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1 NHAA protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.

AB - The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1NHAA. The BF1NHAA protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1 NHAA protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.

KW - BF1

KW - Brain development

KW - Foxg1

KW - Neocortex

KW - Neurogenesis

KW - Telencephalon

KW - Winged helix

UR - http://www.scopus.com/inward/record.url?scp=0036703468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036703468&partnerID=8YFLogxK

M3 - Article

C2 - 12151532

AN - SCOPUS:0036703468

VL - 22

SP - 6526

EP - 6536

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 15

ER -