An ancient role for Gata-1/2/3 and Scl transcription factor homologs in the development of immunocytes

Abstract

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.

Signal-dependent regulation of the sea urchin skeletogenic gene regulatory network

“…At post-gastrula stages, however, many of these same mRNAs, in addition to their ventral expression, begin to accumulate dorsally, eventually accumulating to high levels at the posterior apex of the larva, where the scheitel will form. Other recent studies have also documented elevated expression of mRNAs in the dorsal region at post-gastrula stages (Luo and Su, 2012;Solek et al, 2013). VEGF3 is not expressed dorsally and the expression of genes in this region of the PMC syncytium is unaffected by axitinib; these findings indicate that a different signaling pathway functions in this region.…”

NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily divergent calmodulin-dependent mechanisms

“…We found that S. purpuratus nadk was broadly expressed until the pluteus stage, after which nadk expression became more pronounced in part of the ciliary band, gut, and vertex (a tissue structure of unknown function that accumulates hematopoietic transcription factors typically expressed in immunocytes) (14) (Fig. 2A).…”

ABCC5 is required for cAMP-mediated hindgut invagination in sea urchin embryos

“…Pigment cells are mesodermal immunocytes (Solek et al, 2013) that emerge from the archenteron during gastrulation and distribute throughout the aboral ectoderm Burke, 1985, 1987;Ransick and Davidson, 2006). Cells expressing C5a protein ingress during early gastrulation (Fig.…”

“…Blastocoelar cells are derived from the oral NSM, whereas the aboral NSM gives rise to pigment cells (Ruffins and Ettensohn, 1996). Both pigment and blastocoelar cells generate larval immunocytes (Solek et al, 2013), but their regulatory states are distinct (Materna et al, 2013;Solek et al, 2013).…”