• Share

Ancestral state reconstruction by comparative analysis of a GRN kernel operating in echinoderms
Citation: Erkenbrack, E. M., Ako-Asare, K., Miller, E., Tekelenburg, S., Thompson, J. R., & Romano, L. (2016). Ancestral state reconstruction by comparative analysis of a GRN kernel operating in echinoderms. Development Genes and Evolution, 226(1), 37-45.
Diverse sampling of organisms across the five ma- jor classes in the phylum Echinodermata is beginning to reveal much about the structure and function of gene regulatory net- works (GRNs) in development and evolution. Sea urchins are the most studied clade within this phylum, and recent work suggests there has been dramatic rewiring at the top of the skeletogenic GRN along the lineage leading to extant mem- bers of the euechinoid sea urchins. Such rewiring likely ac- counts for some of the observed developmental differences between the two major subclasses of sea urchins—cidaroids and euechinoids. To address effects of topmost rewiring on downstream GRN events, we cloned four downstream regu- latory genes within the skeletogenic GRN and surveyed their spatiotemporal expression patterns in the cidaroid Eucidaris tribuloides. We performed phylogenetic analyses with homo- logs from other non-vertebrate deuterostomes and character- ized their spatiotemporal expression by quantitative polymer- ase chain reaction (qPCR) and whole-mount in situ hybridi- zation (WMISH). Our data suggest the erg–hex–tgif subcircuit, a putative GRN kernel, exhibits a mesoderm- specific expression pattern early in Eucidaris development that is directly downstream of the initial mesodermal GRN circuitry. Comparative analysis of the expression of this subcircuit in four echinoderm taxa allowed robust ancestral state reconstruction, supporting hypotheses that its ancestral function was to stabilize the mesodermal regulatory state and that it has been co-opted and deployed as a unit in mesodermal subdomains in distantly diverged echinoderms. Importantly, our study supports the notion that GRN kernels exhibit struc- tural and functional modularity, locking down and stabilizing clade-specific, embryonic regulatory states.

More Publications

Decidualization of Human Endometrial Stromal Fibroblasts is a Multiphasic Process Involving Distinct Transcriptional Programs

Decidual stromal cells differentiate from endometrial stromal fibroblasts (ESFs) under the influence of progesterone and cyclic adenosine monophosphate (cAMP) and are essential for implantation and the maintenance of pregnancy. They evolved in the stem lineage of placental (eutherian) mammals coincidental with the evolution of implantation. Here we use the well-established in vitro decidualization protocol to compare early (3 days) and late (8 days) gene transcription patterns in immortalized human ESF. We document extensive, dynamic changes in the early and late decidual cell transcriptomes. The data suggest the existence of an early signal transducer and activator of transcription (STAT) pathway dominated state and a later nuclear factor kB (NFKB) pathway regulated state. Transcription factor expression in both phases is characterized by putative or known progesterone receptor (PGR) target genes, suggesting that both phases are under progesterone control. Decidualization leads to proliferative quiescence, which is reversible by progesterone withdrawal after 3 days but to a lesser extent after 8 days of decidualization. In contrast, progesterone withdrawal induces cell death at comparable levels after short or long exposure to progestins and cAMP. We conclude that decidualization is characterized by a biphasic gene expression dynamic that likely corresponds to different phases in the establishment of the fetal–maternal interface.

A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity Between HOXA11 and FOXO1

Transcription factors (TFs) play multiple roles in development. Given this multifunctionality, it has been assumed that TFs are evolutionarily highly constrained. Here, we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires interaction with FOXO1, and that the physical interaction between these proteins evolved before their functional cooperativity. Here, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex.
© 2016 Eric M Erkenbrack and SpringerNature. All rights reserved.