Charles A. Ettensohn
611B Mellon Institute
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
Ph.D., Yale University
Postdoctoral Appointment, Duke University
We are interested in understanding how the genome encodes the program of development. During embryogenesis, linear (one-dimensional) information contained in the genomic DNA sequence is translated into multicellular (three-dimensional) form. We study this problem using the sea urchin embryo as an experimental model. The complete sequence of the sea urchin genome has been determined and powerful tools are available for manipulating and analyzing gene expression. The rapid, external development and optical transparency of this embryo make it ideally suited to studies of dynamic cell and molecular processes in vivo. The ability to raise large numbers of synchronously developing embryos facilitates molecular biological and biochemical approaches. Lastly, echinoderms are close relatives of vertebrates and many features of their early development are highly conserved.
Our research focuses on three fundamental processes: 1) early patterning, 2) morphogenesis, and 3) the control of development by gene regulatory networks. With respect to the first, we are studying a highly conserved, ancient molecular pathway (the canonical Wnt/beta-catenin pathway) that operates during early development to polarize the embryo. With respect to the problem of morphogenesis, our research focuses on gastrulation and the assembly and patterning of the skeletal system. These processes involve several fundamental cell behaviors, including epithelial-mesenchymal transition, directional cell migration, cell-cell fusion, epithelial invagination, and epithelial cell rearrangement. Lastly, we study transcriptional gene regulatory networks (GRNs) that drive early development. GRNs can be thought of as complex, interconnected systems of interacting genes that influence each other's expression. We are interested in the architecture, developmental function, and evolution of GRNs.
To study these problems, our laboratory uses many different cell biological, molecular biological, genomics-based, and embryological approaches. These include embryo micromanipulation, in vivo protein tagging, targeted protein mutagenesis, cell isolation and culture, perturbation of gene expression by injection of mRNAs and morpholino antisense oligoinucleotides, protein biochemistry, immunochemical methods, large-scale DNA sequencing, and microarray analysis. Modern, fluorescence-based light optical technologies are used to analyze cell behavior and molecular dynamics.
Pittsburgh Developmental Mechanisms Group (PDMG):
Khor JM, Guerrero-Santoro J, Douglas W, Ettensohn CA. Global patterns of enhancer activity during sea urchin embryogenesis assessed by eRNA profiling. Genome Res. 2021 Jul 30:gr.275684.121. doi: 10.1101/gr.275684.121. Epub ahead of print. PMID: 34330790
Guerrero-Santoro J, Khor JM, Açıkbaş AH, Jaynes JB, Ettensohn CA. Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms. J Biol Chem. 2021 Jul;297(1):100901. doi: 10.1016/j.jbc.2021.100901. Epub 2021 Jun 19. PMID: 34157281
Bardhan A, Deiters A, Ettensohn CA. Conditional gene knockdowns in sea urchins using caged morpholinos. Dev Biol. 2021 Jul;475:21-29. doi: 10.1016/j.ydbio.2021.02.014. Epub 2021 Mar 5. PMID: 33684434
Ettensohn CA. The gene regulatory control of sea urchin gastrulation. Mech Dev. 2020 Jun;162:103599. doi: 10.1016/j.mod.2020.103599. Epub 2020 Feb 28. PMID: 32119908
Khor JM, Ettensohn CA. Transcription factors of the Alx family: evolutionarily conserved regulators of deuterostome skeletogenesis. Front Genet. 2020 Nov 23;11:569314. doi: 10.3389/fgene.2020.569314. PMID: 33329706
Ettensohn CA, Adomako-Ankomah A. (2019) The evolution of a new cell type was associated with competition for a signaling ligand. PLoS Biol. 17:e3000460.
Khor JM, Guerrero-Santoro J, Ettensohn CA. (2019) Genome-wide identification of binding sites and gene targets of Alx1, a pivotal regulator of echinoderm skeletogenesis. Development 146: pii: dev180653.
Shashikant T, Ettensohn CA. (2019) Genome-wide analysis of chromatin accessibility using ATAC-seq. Methods Cell Biol. 151:219-235.
Buckley KM, Ettensohn CA. (2019) Techniques for analyzing gene expression using BAC-based reporter constructs. Methods Cell Biol. 151:197-218.
Shashikant T, Khor JM, Ettensohn CA. From Genome to Anatomy: The Architecture and Evolution of the Skeletogenic Gene Regulatory Network of Sea Urchins and Other Echinoderms. Genesis. 2018 Sep 27. doi: 10.1002/dvg.23253. Review. PMID: 30264451
Ettensohn CA. Horizontal transfer of the msp130 gene supported the evolution of metazoan biomineralization. Evol Dev. 2014 May;16(3):139-48.
Adomako-Ankomah A, Ettensohn CA. Growth factors and early mesoderm morphogenesis: insights from the sea urchin embryo. Genesis. 2014 Mar;52(3):158-72.
Rafiq K, Shashikant T, McManus CJ, Ettensohn CA. Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins. Development. 2014 Feb;141(4):950-61.
Rafiq K, Cheers M, and Ettensohn CA. The genomic regulatory control of skeletal morphogenesis in the sea urchin. Development, 2011, in press.
Flynn CJ, Sharma T, Ruffins SW, Guerra SL, Crowley JC, and Ettensohn CA. High-resolution, three-dimensional mapping of gene expression using GeneExpressMap (GEM). Dev. Biol. 357:532-540, 2011.
Sharma T, and Ettensohn CA. Regulative deployment of the skeletogenic gene regulatory network during sea urchin development. Development 138:2581-2590, 2011.
Adomako-Ankomah A., and Ettensohn CA. P58-A and P58-B: novel proteins that mediate skeletogenesis in the sea urchin embryo. Dev. Biol. 353:81-93, 2011.
Stamateris RE, Rafiq K, Ettensohn CA. The expression and distribution of Wnt and Wnt receptor mRNAs during early sea urchin development. Gene Expr. Patterns 10: 60-64, 2010.
Sharma T, and Ettensohn CA. Activation of the skeletogenic gene regulatory network in the early sea urchin embryo. Development 137: 1149-1157, 2010.
Hodor PG and Ettensohn CA. Mesenchymal cell fusion in the sea urchin embryo. Meth. Mol. Biol., 475, 315-334, 2008.
Leonard J and Ettensohn CA. Analysis of dishevelled localization and function in the early sea urchin embryo. Dev. Biol., 306, 50-65, 2007.
Livingston BT, Killian CE, Wilt F, Cameron A, Landrum MJ, Ermolaeva O, Sapojnikov V, Maglott DR, Buchanan AM, Ettensohn CA. A genome-wide analysis of biomineralization-related proteins in the sea urchin, Strongylocentrotus purpuratus. Dev. Biol., 300, 335-348, 2006.