YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation

Zhihui Huang, Jinxia Hu, Jinxiu Pan, Ying Wang, Guoqing Hu, Jiliang Zhou, Lin Mei, Wencheng Xiong

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

YAP (yes-associated protein), a key transcriptional co-factor that is negatively regulated by the Hippo pathway, is crucial for the development and size control of multiple organs, including the liver. However, its role in the brain remains unclear. Here, we provide evidence for YAP regulation of mouse neocortical astrocytic differentiation and proliferation. YAP was undetectable in neurons, but selectively expressed in neural stem cells (NSCs) and astrocytes. YAP in NSCs was required for neocortical astrocytic differentiation, with no apparent role in self-renewal or neural differentiation. However, YAP in astrocytes was necessary for astrocytic proliferation. Yap (Yap1) knockout, Yapnestin conditional knockout and YapGFAP conditional knockout mice displayed fewer neocortical astrocytes and impaired astrocytic proliferation and, consequently, death of neocortical neurons. Mechanistically, YAP was activated by BMP2, and the active/nuclear YAP was crucial for BMP2 induction and stabilization of SMAD1 and astrocytic differentiation. Expression of SMAD1 in YAP-deficient NSCs partially rescued the astrocytic differentiation deficit in response to BMP2. Taken together, these results identify a novel function of YAP in neocortical astrocytic differentiation and proliferation, and reveal a BMP2-YAP-SMAD1 pathway underlying astrocytic differentiation in the developing mouse neocortex.

Original languageEnglish (US)
Pages (from-to)2398-2409
Number of pages12
JournalDevelopment (Cambridge)
Volume143
Issue number13
DOIs
StatePublished - Jul 1 2016

Fingerprint

Proteins
Neural Stem Cells
Astrocytes
Neurons
Neocortex
Knockout Mice
Liver
Brain

Keywords

  • Astrocytes
  • BMP2
  • Differentiation
  • Proliferation
  • SMAD1
  • YAP

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation. / Huang, Zhihui; Hu, Jinxia; Pan, Jinxiu; Wang, Ying; Hu, Guoqing; Zhou, Jiliang; Mei, Lin; Xiong, Wencheng.

In: Development (Cambridge), Vol. 143, No. 13, 01.07.2016, p. 2398-2409.

Research output: Contribution to journalArticle

Huang, Z, Hu, J, Pan, J, Wang, Y, Hu, G, Zhou, J, Mei, L & Xiong, W 2016, 'YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation', Development (Cambridge), vol. 143, no. 13, pp. 2398-2409. https://doi.org/10.1242/dev.130658
Huang, Zhihui ; Hu, Jinxia ; Pan, Jinxiu ; Wang, Ying ; Hu, Guoqing ; Zhou, Jiliang ; Mei, Lin ; Xiong, Wencheng. / YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation. In: Development (Cambridge). 2016 ; Vol. 143, No. 13. pp. 2398-2409.
@article{44e4e7f830584b41aebd1f486cdfe33c,
title = "YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation",
abstract = "YAP (yes-associated protein), a key transcriptional co-factor that is negatively regulated by the Hippo pathway, is crucial for the development and size control of multiple organs, including the liver. However, its role in the brain remains unclear. Here, we provide evidence for YAP regulation of mouse neocortical astrocytic differentiation and proliferation. YAP was undetectable in neurons, but selectively expressed in neural stem cells (NSCs) and astrocytes. YAP in NSCs was required for neocortical astrocytic differentiation, with no apparent role in self-renewal or neural differentiation. However, YAP in astrocytes was necessary for astrocytic proliferation. Yap (Yap1) knockout, Yapnestin conditional knockout and YapGFAP conditional knockout mice displayed fewer neocortical astrocytes and impaired astrocytic proliferation and, consequently, death of neocortical neurons. Mechanistically, YAP was activated by BMP2, and the active/nuclear YAP was crucial for BMP2 induction and stabilization of SMAD1 and astrocytic differentiation. Expression of SMAD1 in YAP-deficient NSCs partially rescued the astrocytic differentiation deficit in response to BMP2. Taken together, these results identify a novel function of YAP in neocortical astrocytic differentiation and proliferation, and reveal a BMP2-YAP-SMAD1 pathway underlying astrocytic differentiation in the developing mouse neocortex.",
keywords = "Astrocytes, BMP2, Differentiation, Proliferation, SMAD1, YAP",
author = "Zhihui Huang and Jinxia Hu and Jinxiu Pan and Ying Wang and Guoqing Hu and Jiliang Zhou and Lin Mei and Wencheng Xiong",
year = "2016",
month = "7",
day = "1",
doi = "10.1242/dev.130658",
language = "English (US)",
volume = "143",
pages = "2398--2409",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "13",

}

TY - JOUR

T1 - YAP stabilizes SMAD1 and promotes BMP2-induced neocortical astrocytic differentiation

AU - Huang, Zhihui

AU - Hu, Jinxia

AU - Pan, Jinxiu

AU - Wang, Ying

AU - Hu, Guoqing

AU - Zhou, Jiliang

AU - Mei, Lin

AU - Xiong, Wencheng

PY - 2016/7/1

Y1 - 2016/7/1

N2 - YAP (yes-associated protein), a key transcriptional co-factor that is negatively regulated by the Hippo pathway, is crucial for the development and size control of multiple organs, including the liver. However, its role in the brain remains unclear. Here, we provide evidence for YAP regulation of mouse neocortical astrocytic differentiation and proliferation. YAP was undetectable in neurons, but selectively expressed in neural stem cells (NSCs) and astrocytes. YAP in NSCs was required for neocortical astrocytic differentiation, with no apparent role in self-renewal or neural differentiation. However, YAP in astrocytes was necessary for astrocytic proliferation. Yap (Yap1) knockout, Yapnestin conditional knockout and YapGFAP conditional knockout mice displayed fewer neocortical astrocytes and impaired astrocytic proliferation and, consequently, death of neocortical neurons. Mechanistically, YAP was activated by BMP2, and the active/nuclear YAP was crucial for BMP2 induction and stabilization of SMAD1 and astrocytic differentiation. Expression of SMAD1 in YAP-deficient NSCs partially rescued the astrocytic differentiation deficit in response to BMP2. Taken together, these results identify a novel function of YAP in neocortical astrocytic differentiation and proliferation, and reveal a BMP2-YAP-SMAD1 pathway underlying astrocytic differentiation in the developing mouse neocortex.

AB - YAP (yes-associated protein), a key transcriptional co-factor that is negatively regulated by the Hippo pathway, is crucial for the development and size control of multiple organs, including the liver. However, its role in the brain remains unclear. Here, we provide evidence for YAP regulation of mouse neocortical astrocytic differentiation and proliferation. YAP was undetectable in neurons, but selectively expressed in neural stem cells (NSCs) and astrocytes. YAP in NSCs was required for neocortical astrocytic differentiation, with no apparent role in self-renewal or neural differentiation. However, YAP in astrocytes was necessary for astrocytic proliferation. Yap (Yap1) knockout, Yapnestin conditional knockout and YapGFAP conditional knockout mice displayed fewer neocortical astrocytes and impaired astrocytic proliferation and, consequently, death of neocortical neurons. Mechanistically, YAP was activated by BMP2, and the active/nuclear YAP was crucial for BMP2 induction and stabilization of SMAD1 and astrocytic differentiation. Expression of SMAD1 in YAP-deficient NSCs partially rescued the astrocytic differentiation deficit in response to BMP2. Taken together, these results identify a novel function of YAP in neocortical astrocytic differentiation and proliferation, and reveal a BMP2-YAP-SMAD1 pathway underlying astrocytic differentiation in the developing mouse neocortex.

KW - Astrocytes

KW - BMP2

KW - Differentiation

KW - Proliferation

KW - SMAD1

KW - YAP

UR - http://www.scopus.com/inward/record.url?scp=84977080476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84977080476&partnerID=8YFLogxK

U2 - 10.1242/dev.130658

DO - 10.1242/dev.130658

M3 - Article

C2 - 27381227

AN - SCOPUS:84977080476

VL - 143

SP - 2398

EP - 2409

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 13

ER -