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embryos & evolution

Welcome to my home for science commentary, research highlights, articles, and just about anything I want to keep track of. This site also acts as a repository for current and past research, as well as serving as my interactive CV. Thank you for visiting.

email: eric.erkenbrack(a)yale.edu
About me
Current position: Charles H Revson Senior Fellow in Biomedical Sciences, Systems Biology Institute, Yale University.

Current Research: Cell type origination and molecular basis of novelty during the evolution of mammalian reproduction, Laboratory of Günter Wagner, Department of Ecology and Evolutionary Biology, Yale University.

Previous position: Postdoctoral Associate, Laboratory of Günter Wagner.

PhD Dissertation: Evolution of gene regulatory networks in early sea urchin development, Laboratory of Eric H Davidson, California Institute of Technology.

My research/academic interests are developmental evolution, comparative embryology, history of biology, gene regulation, and cell type evolution.

2008 - 2016, California Institute of Technology: PhD, Biological Sciences
2005 - 2008, Tufts University: BA, Philosophy & BS, Biology
2006 - 2007, Eberhard Karls Universität Tübingen, Germany 
2003 - 2005, Normandale Community College

View Academic Tree
  • Geological Society of America, September 2016:
  • Society of Developmental Biology, August 2016:
Invited Speaker: Evolution, Development and Paleogenomics (Session)

Poster: Comparative analysis of global regulatory gene deployment reveals tempo and mode of alterations to developmental gene regulatory networks in echinoids

Stress-induced evolutionary innovation: A mechanism for the origin of cell types

Cells frequently counteract environmental stress by conserved molecular mechanisms, leading to stress mitigation or apoptosis. Increasingly, studies on cellular stress responses intersect with cell type differentiation programs. It is hypothesized that integration of these conserved pathways is a mechanism of stress‐induced evolutionary innovation that is capable of generating novel cell types.

Conserved regulatory state expression controlled by divergent developmental gene regulatory networks in echinoids

Evolution of the animal body plan is driven by changes in developmental gene regulatory networks (GRNs), but how networks change to control novel developmental phenotypes remains in most cases unresolved. Here we address GRN evolution by comparing the endomesoderm GRN in two echinoid sea urchins, Strongylocentrotus purpuratus and Eucidaris tribuloides, with at least 268 million years of independent evolution. We first analyzed the expression of twelve transcription factors and signaling molecules of the S. purpuratus GRN in E. tribuloides embryos, showing that orthologous regulatory genes are expressed in corresponding endomesodermal cell fates in the two species. However, perturbation of regulatory genes revealed that important regulatory circuits of the S. purpuratus GRN are significantly different in E. tribuloides. Thus for instance mesodermal Delta/Notch signaling controls exclusion of alternative cell fates in E. tribuloides but controls mesoderm induction and activation of a positive feedback circuit in S. purpuratus. These results indicate that the architecture of the sea urchin endomesoderm GRN evolved by extensive gain and loss of regulatory interactions between a conserved set of regulatory factors that control endomesodermal cell fate specification.

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.

The mammalian decidual cell evolved from a cellular stress response

Animals consist of a wide variety of cells that serve different functions depending on their location in the body. Cells with similar functions, or cell types, in different animal species are related both by an evolutionary line of descentÐsimilar to the relatedness of species themselvesÐand by a developmental line of descent in the embryo. Networks of interacting genes, or gene regulatory networks, control gene expression in the cell, thereby specifying cell type identity. Understanding how new cell types arise by changing gene regulatory networks is critical both to comprehending fundamental aspects of human biology and to manipulating cell types in the laboratory. We approached this question by studying endometrial stromal fibroblast (ESF) cells from the uterus of humans and opossums, two distantly related mammals. We showed that the distantly related cell type in opossum expresses a similar set of regulatory genes as the human cell, but in response to pregnancy-related signals, the opossum cells induce a stress response. In the human cells, these signals induce differentiation into decidual cells, a specialized cell type present in humans and closely related mammals. These results suggest that a gene regulatory network that modulated an ancestral, pregnancy-related stress response was hijacked and repurposed to function in differentiation and specification of the decidual cell type.

Notch-mediated lateral inhibition is an evolutionarily conserved mechanism patterning the ectoderm of echinoids

Notch signaling is a crucial cog in early development of euechinoid sea urchins, specifying both non-skeletogenic mesodermal lineages and serotonergic neurons in the apical neuroectoderm. Here, the spatial distributions and function of delta, gcm, and hesc, three genes critical to these processes in euechinoids, are examined in the distantly related cidaroid sea urchin Eucidaris tribuloides. Spatial distribution and experimental perturbation of delta and hesc suggest that the function of Notch signaling in ectodermal patterning in early development of E. tribuloides is consistent with canonical lateral inhibition. Delta transcripts were observed in the archenteron, apical ectoderm, and lateral ectoderm in gastrulating embryos of E. tribuloides. Perturbation of Notch signaling by either delta morpholino or treatment of DAPT downregulated hesc and upregulated delta and gcm, resulting in ectopic expression of delta and gcm. Similarly, hesc perturbation mirrored the effects of delta perturbation. Interestingly, perturbation of delta or hesc resulted in more cells expressing gcm and supernumerary pigment cells, suggesting that pigment cell proliferation is regulated by Notch in E. tribuloides. These results are consistent with an evolutionary scenario whereby, in the echinoid ancestor, Notch signaling was deployed in the ectoderm to specify neurogenic progenitors and controlled pigment cell proliferation in the dorsal ectoderm.

Explaining genome size to my 3 year old daughter

Genomes are huge. My 3-year-old daughter and I had a discussion about this. We came to the conclusion that it would take approximately 165 years to "stamp out" the human genome with her new stamping pad set. She was impressed!

What is development?

All of the creatures you see with the unaided eye have undergone the process of development. Adults come from eggs, and eggs come from adults. It is necessarily circular, as cells come from cells. The egg is nothing more than a cell. In fact, the largest cell on the planet is an egg--an ostrich egg.
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PLOS Biology Feature
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An Interactive CV

Eric M Erkenbrack
Yale University
eric.erkenbrack (at) yale.edu