Bid Expression Network Controls Neuronal Cell Fate During Avian Ciliary Ganglion Development

Frontiers in Physiology

卷:9

Kerstin Krieglstein¹  Veronica La Padula²  Sophie Koszinowski²  Melanie Boerries⁴  Frank Edlich⁵  Hauke Busch⁶ 

[1] Department of Molecular Embryology, Institute of Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany;

[2] Faculty of Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany;

[3] German Cancer Consortium (DKTK), Freiburg, Germany;

[4] German Cancer Research Center (DKFZ), Heidelberg, Germany;

[5] Institute for Biochemistry and Molecular Biology, and Centre for Biological Signalling Studies BIOSS, Albert-Ludwigs-University Freiburg, Freiburg, Germany;

[6] Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany;

[7] Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Freiburg, Germany;

[8] Luebeck Institute for Experimental Dermatology, University of Lübeck, Lübeck, Germany;

关键词: network inference;    protein interaction network;    ontogenetic cell death;    neuronal development;    BID;    time series analysis;   

DOI  :  10.3389/fphys.2018.00797

来源: DOAJ

【 摘 要 】

Avian ciliary ganglion (CG) development involves a transient execution phase of apoptosis controlling the final number of neurons, but the time-dependent molecular mechanisms for neuronal cell fate are largely unknown. To elucidate the molecular networks regulating important aspects of parasympathetic neuronal development, a genome-wide expression analysis was performed during multiple stages of avian CG development between embryonic days E6 and E14. The transcriptome data showed a well-defined sequence of events, starting from neuronal migration via neuronal fate cell determination, synaptic transmission, and regulation of synaptic plasticity to growth factor associated signaling. In particular, we extracted a neuronal apoptosis network that characterized the cell death execution phase at E8/E9 and apoptotic cell clearance at E14 by combining the gene time series analysis with network synthesis from the chicken interactome. Network analysis identified TP53 as key regulator and predicted involvement of the BH3 interacting domain death agonist (BID). A virus-based RNAi knockdown approach in vivo showed a crucial impact of BID expression on the execution of ontogenetic programmed cell death (PCD). In contrast, Bcl-XL expression did not impact PCD. Therefore, BID-mediated apoptosis represents a novel cue essential for timing within CG maturation.

【 授权许可】

Unknown