Sunnybrook Research Institute and Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Room S-126B, Toronto, Ontario, Canada M4N 3M5.
Dev Biol. 2013 Oct 1;382(1):280-92. doi: 10.1016/j.ydbio.2013.06.019. Epub 2013 Jun 20.
Although vertebrate hematopoiesis is the focus of intense study, immunocyte development is well-characterized in only a few invertebrate groups. The sea urchin embryo provides a morphologically simple model for immune cell development in an organism that is phylogenetically allied to vertebrates. Larval immunocytes, including pigment cells and several blastocoelar cell subtypes, emerge from a population of non-skeletal mesodermal (NSM) precursors that is specified at the blastula stage. This ring of cells is first partitioned into oral and aboral fields with distinct blastocoelar and pigment cell gene regulatory programs. The oral field is subsequently specified into several distinct immune and non-immune cell types during gastrulation. Here we characterize the oral NSM expression and downstream function of two homologs of key vertebrate hematopoietic transcription factors: SpGatac, an ortholog of vertebrate Gata-1/2/3 and SpScl, an ortholog of Scl/Tal-2/Lyl-1. Perturbation of SpGatac affects blastocoelar cell migration at gastrulation and later expression of immune effector genes, whereas interference with SpScl function disrupts segregation of pigment and blastocoelar cell precursors. Homologs of several transcription regulators that interact with Gata-1/2/3 and Scl factors in vertebrate hematopoiesis are also co-expressed in the oral NSM, including SpE-protein, the sea urchin homolog of vertebrate E2A/HEB/E2-2 and SpLmo2, an ortholog of a dedicated cofactor of the Scl-GATA transcription complex. Regulatory analysis of SpGatac indicates that oral NSM identity is directly suppressed in presumptive pigment cells by the transcription factor SpGcm. These findings provide part of a comparative basis to understand the evolutionary origins and regulatory biology of deuterostome immune cell differentiation in the context of a tractable gene regulatory network model.
尽管脊椎动物造血是研究的焦点，但只有少数无脊椎动物群体的免疫细胞发育得到了很好的描述。海胆胚胎为在与脊椎动物系统发育相关的生物体中免疫细胞发育提供了一个形态简单的模型。幼虫免疫细胞，包括色素细胞和几种囊胚腔细胞亚型，由一群非骨骼中胚层 (NSM) 前体发育而来，这些前体在囊胚阶段被指定。这些细胞首先被划分为口腔和咽腔两个区域，具有不同的囊胚腔和色素细胞基因调控程序。随后，在原肠胚形成过程中，口腔区域被进一步指定为几种不同的免疫和非免疫细胞类型。在这里，我们描述了两个关键脊椎动物造血转录因子同源物在口腔 NSM 中的表达和下游功能：SpGatac，脊椎动物 Gata-1/2/3 的同源物，以及 SpScl，Scl/Tal-2/Lyl-1 的同源物。SpGatac 的扰动会影响原肠胚形成时囊胚腔细胞的迁移和随后免疫效应基因的表达，而干扰 SpScl 功能会破坏色素细胞和囊胚腔细胞前体的分离。与脊椎动物造血中 Gata-1/2/3 和 Scl 因子相互作用的几个转录调节剂的同源物也在口腔 NSM 中共同表达，包括 SpE-protein，脊椎动物 E2A/HEB/E2-2 的同源物，以及 SpLmo2，Scl-GATA 转录复合物的专用辅因子的同源物。SpGatac 的调控分析表明，口腔 NSM 身份直接被转录因子 SpGcm 在假定的色素细胞中抑制。这些发现为了解后生动物免疫细胞分化的进化起源和调控生物学提供了部分比较基础，这是在可处理的基因调控网络模型的背景下进行的。
