Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, California 94143, USA.
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Nat Commun. 2017 Jul 27;8:15990. doi: 10.1038/ncomms15990.
An outstanding question in animal development, tissue homeostasis and disease is how cell populations adapt to sensory inputs. During Drosophila larval development, hematopoietic sites are in direct contact with sensory neuron clusters of the peripheral nervous system (PNS), and blood cells (hemocytes) require the PNS for their survival and recruitment to these microenvironments, known as Hematopoietic Pockets. Here we report that Activin-β, a TGF-β family ligand, is expressed by sensory neurons of the PNS and regulates the proliferation and adhesion of hemocytes. These hemocyte responses depend on PNS activity, as shown by agonist treatment and transient silencing of sensory neurons. Activin-β has a key role in this regulation, which is apparent from reporter expression and mutant analyses. This mechanism of local sensory neurons controlling blood cell adaptation invites evolutionary parallels with vertebrate hematopoietic progenitors and the independent myeloid system of tissue macrophages, whose regulation by local microenvironments remain undefined.
在动物发育、组织稳态和疾病领域,一个悬而未决的问题是细胞群体如何适应感觉输入。在果蝇幼虫发育过程中,造血部位与外周神经系统 (PNS) 的感觉神经元簇直接接触,血细胞 (hemocytes) 需要 PNS 才能存活并募集到这些称为造血口袋的微环境中。在这里,我们报告说,Activin-β,一种 TGF-β 家族配体,由 PNS 的感觉神经元表达,并调节 hemocytes 的增殖和黏附。这些 hemocyte 反应依赖于 PNS 的活性,如激动剂处理和感觉神经元的瞬时沉默所示。Activin-β 在这种调节中起着关键作用,这可以从报告基因表达和突变分析中看出。这种局部感觉神经元控制血细胞适应性的机制与脊椎动物造血祖细胞和组织巨噬细胞的独立髓样系统相类似,其局部微环境的调节尚不清楚。