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About

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.

EDUCATION
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

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Conferences
  • 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
Publications

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.

Paleogenomics of echinoids reveals an ancient origin for the double-negative specification of micromeres in sea urchins

Establishing a timeline for the evolution of novelties is a common, unifying goal at the intersection of evolutionary and developmental biology. Analyses of gene regulatory networks (GRNs) provides the ability to understand the underlying genetic and developmental mechanisms responsible for the origin of morphological structures both in the development of an individual and across entire evolutionary lineages. Accurately dating GRN novelties, thereby establishing a timeline for GRN evolution, is necessary to answer questions about the rate at which GRNs and their subcircuits evolve, and to tie their evolution to paleoenvironmental and paleoecological changes. Paleogenomics unites the fossil record and all aspects of deep time, with modern genomics and developmental biology to understand the evolution of genomes in evolutionary time. Recent work on the regulatory genomic basis of development in cidaroid echinoids, sand dollars, heart urchins, and other nonmodel echinoderms provides an ideal dataset with which to explore GRN evolution in a comparative framework. Using divergence time estimation and ancestral state reconstructions, we have determined the age of the double-negative gate (DNG), the subcircuit which specifies micromeres and skeletogenic cells in Strongylocentrotus purpuratus. We have determined that the DNG has likely been used for euechinoid echinoid micromere specification since at least the Late Triassic. The innovation of the DNG thus predates the burst of post-Paleozoic echinoid morphological diversification that began in the Early Jurassic. Paleogenomics has wide applicability for the integration of deep time and molecular developmental data, and has wide utility in rigorously establishing timelines for GRN evolution.

Divergence of ectodermal and mesodermal gene regulatory network linkages in early development of sea urchins

Developmental gene regulatory networks (GRNs) are assemblages of gene regulatory interactions that direct ontogeny of animal body plans. Studies of GRNs operating in the early development of euechinoid sea urchins have revealed that little appreciable change has occurred since their divergence ∼90 million years ago (mya). These observations suggest that strong conservation of GRN architecture was maintained in early development of the sea urchin lineage. Testing whether this holds for all sea urchins necessitates comparative analyses of echinoid taxa that diverged deeper in geological time. Recent studies highlighted extensive divergence of skeletogenic mesoderm specification in the sister clade of euechinoids, the cidaroids, suggesting that comparative analyses of cidaroid GRN architecture may confer a greater understanding of the evolutionary dynamics of developmental GRNs. Here I report spatiotemporal patterning of 55 regulatory genes and perturbation analyses of key regulatory genes involved in euechinoid oral–aboral patterning of nonskeletogenic mesodermal and ectodermal domains in early development of the cidaroid Eucidaris tribuloides. These results indicate that developmental GRNs directing mesodermal and ectodermal specification have undergone marked alterations since the divergence of cidaroids and euechinoids. Notably, statistical and clustering analyses of echinoid temporal gene expression datasets indicate that regulation of mesodermal genes has diverged more markedly than regulation of ectodermal genes. Although research on indirect-developing euechinoid sea urchins suggests strong conservation of GRN circuitry during early embryogenesis, this study indicates that since the divergence of cidaroids and euechinoids, developmental GRNs have undergone significant, cell type–biased alterations.

A Conserved Role for VEGF Signaling in Specification of Homologous Mesenchymal Cell Types Positioned at Spatially Distinct Developmental Addresses in Early Development of Sea Urchins

Comparative studies of early development in echinoderms are revealing the tempo and mode of alterations to developmental gene regulatory networks and to the cell types they specify. In euechinoid sea urchins, skeletogenic mesenchyme (SM) ingresses prior to gastrulation at the vegetal pole and aligns into a ring-like array with two bilateral pockets of cells, the sites where spiculogenesis will later occur. In cidaroid sea urchins, the anciently diverged sister clade to euechinoid sea urchins, a homologous SM cell type ingresses later in development, after gastrulation has commenced, and consequently at a distinct developmental address. Thus, a heterochronic shift of ingression of the SM cell type occurred in one of the echinoid lineages. In euechinoids, speci cation and migration of SM are facilitated by vascular endothelial growth factor (VEGF) signaling. We describe spatiotemporal expression of vegf and vegfr and experimental manipulations target- ing VEGF signaling in the cidaroid Eucidaris tribuloides.
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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!
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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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An Interactive CV

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