Wang Shu, Tulina Natalia, Carlin Daniel L, Rulifson Eric J
Wistar Institute, Room 358, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19873-8. doi: 10.1073/pnas.0707465104. Epub 2007 Dec 3.
Single-cell resolution lineage information is a critical key to understanding how the states of gene regulatory networks respond to cell interactions and thereby establish distinct cell fates. Here, we identify a single pair of neural stem cells (neuroblasts) as progenitors of the brain insulin-producing neurosecretory cells of Drosophila, which are homologous to islet beta cells. Likewise, we identify a second pair of neuroblasts as progenitors of the neurosecretory Corpora cardiaca cells, which are homologous to the glucagon-secreting islet alpha cells. We find that both progenitors originate as neighboring cells from anterior neuroectoderm, which expresses genes orthologous to those expressed in the vertebrate adenohypophyseal placode, the source of endocrine anterior pituitary and neurosecretory hypothalamic cells [Whitlock KE (2005) Trends Endocrinol Metab 16:145-151]. This ontogenic-molecular concordance suggests that a rudimentary brain endocrine axis was present in the common ancestor of humans and flies, where it orchestrated the islet-like endocrine functions of insulin and glucagon biology.
单细胞分辨率的谱系信息是理解基因调控网络状态如何响应细胞间相互作用从而建立不同细胞命运的关键所在。在此,我们鉴定出一对神经干细胞(成神经细胞)作为果蝇脑内产生胰岛素的神经分泌细胞的祖细胞,这些细胞与胰岛β细胞同源。同样,我们鉴定出另一对成神经细胞作为神经分泌性心侧体细胞的祖细胞,这些细胞与分泌胰高血糖素的胰岛α细胞同源。我们发现这两种祖细胞均起源于前神经外胚层的相邻细胞,该前神经外胚层表达的基因与脊椎动物腺垂体原基中表达的基因直系同源,而腺垂体原基是内分泌性垂体前叶和神经分泌性下丘脑细胞的来源[惠特洛克·凯(2005年)《内分泌与代谢趋势》16:145 - 151]。这种个体发生 - 分子一致性表明,人类和果蝇的共同祖先中存在一个原始的脑内分泌轴,在那里它协调了胰岛素和胰高血糖素生物学中类似胰岛的内分泌功能。