The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model

Liankai Chi, Beibei Fan, Dandan Feng, Zhenyu Chen, Zhongliang Liu, Yi Hui, Xiangjie Xu, Lin Ma, Yujiang Fang, Quanbin Zhang, Guohua Jin, Ling Liu, Fangxia Guan, Xiaoqing Zhang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh-driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.

Original languageEnglish (US)
Pages (from-to)2941-2954
Number of pages14
JournalCerebral Cortex
Volume27
Issue number5
DOIs
StatePublished - May 1 2017
Externally publishedYes

Fingerprint

Prosencephalon
Neural Plate
Hedgehogs
Telencephalon
Genes
Intrinsic Factor
Gene Regulatory Networks
Vertebrates
Transcription Factors
Central Nervous System

Keywords

  • Brain development
  • Human embryonic stem cells
  • Neural differentiation
  • Regional patterning
  • Sonic hedgehog
  • Wnts

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Chi, L., Fan, B., Feng, D., Chen, Z., Liu, Z., Hui, Y., ... Zhang, X. (2017). The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model. Cerebral Cortex, 27(5), 2941-2954. https://doi.org/10.1093/cercor/bhw152

The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model. / Chi, Liankai; Fan, Beibei; Feng, Dandan; Chen, Zhenyu; Liu, Zhongliang; Hui, Yi; Xu, Xiangjie; Ma, Lin; Fang, Yujiang; Zhang, Quanbin; Jin, Guohua; Liu, Ling; Guan, Fangxia; Zhang, Xiaoqing.

In: Cerebral Cortex, Vol. 27, No. 5, 01.05.2017, p. 2941-2954.

Research output: Contribution to journalArticle

Chi, L, Fan, B, Feng, D, Chen, Z, Liu, Z, Hui, Y, Xu, X, Ma, L, Fang, Y, Zhang, Q, Jin, G, Liu, L, Guan, F & Zhang, X 2017, 'The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model', Cerebral Cortex, vol. 27, no. 5, pp. 2941-2954. https://doi.org/10.1093/cercor/bhw152
Chi, Liankai ; Fan, Beibei ; Feng, Dandan ; Chen, Zhenyu ; Liu, Zhongliang ; Hui, Yi ; Xu, Xiangjie ; Ma, Lin ; Fang, Yujiang ; Zhang, Quanbin ; Jin, Guohua ; Liu, Ling ; Guan, Fangxia ; Zhang, Xiaoqing. / The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model. In: Cerebral Cortex. 2017 ; Vol. 27, No. 5. pp. 2941-2954.
@article{d5bade5abe6b4ae6b852b61b5a4dd15f,
title = "The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model",
abstract = "The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh-driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.",
keywords = "Brain development, Human embryonic stem cells, Neural differentiation, Regional patterning, Sonic hedgehog, Wnts",
author = "Liankai Chi and Beibei Fan and Dandan Feng and Zhenyu Chen and Zhongliang Liu and Yi Hui and Xiangjie Xu and Lin Ma and Yujiang Fang and Quanbin Zhang and Guohua Jin and Ling Liu and Fangxia Guan and Xiaoqing Zhang",
year = "2017",
month = "5",
day = "1",
doi = "10.1093/cercor/bhw152",
language = "English (US)",
volume = "27",
pages = "2941--2954",
journal = "Cerebral Cortex",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model

AU - Chi, Liankai

AU - Fan, Beibei

AU - Feng, Dandan

AU - Chen, Zhenyu

AU - Liu, Zhongliang

AU - Hui, Yi

AU - Xu, Xiangjie

AU - Ma, Lin

AU - Fang, Yujiang

AU - Zhang, Quanbin

AU - Jin, Guohua

AU - Liu, Ling

AU - Guan, Fangxia

AU - Zhang, Xiaoqing

PY - 2017/5/1

Y1 - 2017/5/1

N2 - The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh-driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.

AB - The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh-driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.

KW - Brain development

KW - Human embryonic stem cells

KW - Neural differentiation

KW - Regional patterning

KW - Sonic hedgehog

KW - Wnts

UR - http://www.scopus.com/inward/record.url?scp=85019087918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019087918&partnerID=8YFLogxK

U2 - 10.1093/cercor/bhw152

DO - 10.1093/cercor/bhw152

M3 - Article

C2 - 27226442

AN - SCOPUS:85019087918

VL - 27

SP - 2941

EP - 2954

JO - Cerebral Cortex

JF - Cerebral Cortex

SN - 1047-3211

IS - 5

ER -