Distinct functions of BMP4 during different stages of mouse ES cell neural commitment

Kejing Zhang, Lingyu Li, Chengyang Huang, Chengyong Shen, Fangzhi Tan, Caihong Xia, Pingyu Liu, Janet Rossant, Naihe Jing

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Bone morphogenetic protein (BMP) signaling plays a crucial role in maintaining the pluripotency of mouse embryonic stem cells (ESCs) and has negative effects on ESC neural differentiation. However, it remains unclear when and how BMP signaling executes those different functions during neural commitment. Here, we show that a BMP4-sensitive window exists during ESC neural differentiation. Cells at this specific period correspond to the egg cylinder stage epiblast and can be maintained as ESC-derived epiblast stem cells (ESD-EpiSCs), which have the same characteristics as EpiSCs derived from mouse embryos. We propose that ESC neural differentiation occurs in two stages: first from ESCs to ESD-EpiSCs and then from ESD-EpiSCs to neural precursor cells (NPCs). We further show that BMP4 inhibits the conversion of ESCs into ESD-EpiSCs during the first stage, and suppresses ESD-EpiSC neural commitment and promotes non-neural lineage differentiation during the second stage. Mechanistic studies show that BMP4 inhibits FGF/ERK activity at the first stage but not at the second stage; and IDs, as important downstream genes of BMP signaling, partially substitute for BMP4 functions at both stages. We conclude that BMP signaling has distinct functions during different stages of ESC neural commitment.

Original languageEnglish (US)
Pages (from-to)2095-2105
Number of pages11
JournalDevelopment
Volume137
Issue number13
DOIs
StatePublished - Jul 1 2010

Fingerprint

Embryonic Stem Cells
Germ Layers
Bone Morphogenetic Proteins
Cell Differentiation
Stem Cells
Neural Stem Cells
Ovum
Embryonic Structures
Genes

Keywords

  • BMP4
  • Embryonic stem cells
  • EpiSCs
  • Epiblasts
  • Mouse
  • Neural commitment

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Zhang, K., Li, L., Huang, C., Shen, C., Tan, F., Xia, C., ... Jing, N. (2010). Distinct functions of BMP4 during different stages of mouse ES cell neural commitment. Development, 137(13), 2095-2105. https://doi.org/10.1242/dev.049494

Distinct functions of BMP4 during different stages of mouse ES cell neural commitment. / Zhang, Kejing; Li, Lingyu; Huang, Chengyang; Shen, Chengyong; Tan, Fangzhi; Xia, Caihong; Liu, Pingyu; Rossant, Janet; Jing, Naihe.

In: Development, Vol. 137, No. 13, 01.07.2010, p. 2095-2105.

Research output: Contribution to journalArticle

Zhang, K, Li, L, Huang, C, Shen, C, Tan, F, Xia, C, Liu, P, Rossant, J & Jing, N 2010, 'Distinct functions of BMP4 during different stages of mouse ES cell neural commitment', Development, vol. 137, no. 13, pp. 2095-2105. https://doi.org/10.1242/dev.049494
Zhang, Kejing ; Li, Lingyu ; Huang, Chengyang ; Shen, Chengyong ; Tan, Fangzhi ; Xia, Caihong ; Liu, Pingyu ; Rossant, Janet ; Jing, Naihe. / Distinct functions of BMP4 during different stages of mouse ES cell neural commitment. In: Development. 2010 ; Vol. 137, No. 13. pp. 2095-2105.
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