New Finding: Distinct functions of BMP4 during different stages of mouse

On May 26, 2010, Development online published a research article entitled "Distinct Functions of BMP4 during Different Stages of Mouse ES Cell Neural Commitment" from Naihe Jing’s group in Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Chinese Academy of Sciences. This work was carried out by graduate students Kejing Zhang and Lingyu Li under the supervision of Prof. Naihe Jing.

 

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. Kejing Zhang and Lingyu Li et al. showed 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. Therefore, they proposed that ESC neural differentiation occurs in two stages: first from ESCs to ESD-EpiSCs and then from ESD-EpiSCs to neural precursor cells (NPCs). They further showed 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 revealed 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.

 

This work was supported by the grants from National Natural Science Foundation of China, the National Key Basic Research and Development Program of China, the Shanghai Key Project of Basic Science Research, and the Council of Shanghai Municipal Government for Science and Technology. (SIBCB)