Genome-wide mRNA expression analyses revealed dysregulation of genes important for sympathetic neuron development in isl1 cko and hypomorphic mutant embryos.

Understanding factors that drive development and function of the sympathetic neuron is crucial to development of potential therapies for neuroblastoma. Here, we identify a key cell autonomous role for the LIM homeodomain transcription factor ISL1 for survival, proliferation and differentiation of sympathetic neurons throughout development. Analysis of several Isl1 mutant mouse lines, including one in which Isl1 was specifically ablated in sympathetic neuron (Wnt1-cre;Isl1 f/f) revealed an early requirement for Isl1 within sympathetic neurons for proliferation and surrvial. RNA-seq analyses on sympathetic neurons revealed dysregulation of a number of genes critical for sympathetic neuron development .Our studies demonstrated that ISL1 regulated the proliferation, survival and differentiation. Expression profiling of sympathetic ganglion dissected from E11.5 or E14.5 wild-type and isl1 mutant embryos.阐明调控交感神经元发育与功能的关键因素，对于开发神经母细胞瘤的潜在治疗方案至关重要。本研究发现，同源域LIM转录因子ISL1在交感神经元的整个发育过程中，对其存活、增殖与分化发挥关键的细胞自主调控作用。我们对多种Isl1突变小鼠品系（包括在交感神经元中特异性敲除Isl1的Wnt1-cre;Isl1 f/f品系）开展分析，结果揭示了交感神经元内Isl1在增殖与存活过程中的早期必需性。对交感神经元进行RNA测序（RNA-seq）分析后，发现大量与交感神经元发育密切相关的基因表达失调。本研究证实，ISL1可调控交感神经元的增殖、存活与分化过程。此外，本研究还对取自E11.5及E14.5野生型与isl1突变胚胎的交感神经节进行了表达谱分析。