Honors & Awards


  • Esther M. Zimmer Lederberg Graduate Fellowship, Hopkins Marine Station (2016)
  • Graduate Research Award, Dr. Earl H Myers & Ethel M. Myers Oceanographic and Marine Biology Trust (2015)
  • Eugene & Aileen Haderlie Award, Hopkins Marine Station (2014)
  • Graduate Research Fellowship, National Science Foundation (NSF) (2013)
  • William R. and Sara Hart Kimball Fellowship, Stanford University (2012)

Stanford Advisors


All Publications


  • Characterization of the Cadherin-Catenin Complex of the Sea Anemone Nematostella vectensis and Implications for the Evolution of Metazoan Cell-Cell Adhesion MOLECULAR BIOLOGY AND EVOLUTION Clarke, D. N., Miller, P. W., Lowe, C. J., Weis, W. I., Nelson, W. J. 2016; 33 (8): 2016-2029

    Abstract

    The cadherin-catenin complex (CCC) mediates cell-cell adhesion in bilaterian animals by linking extracellular cadherin-based adhesions to the actin cytoskeleton. However, it is unknown whether the basic organization of the complex is conserved across all metazoans. We tested whether protein interactions and actin-binding properties of the CCC are conserved in a nonbilaterian animal, the sea anemone Nematostella vectensis We demonstrated that N. vectensis has a complete repertoire of cadherin-catenin proteins, including two classical cadherins, one α-catenin, and one β-catenin. Using size-exclusion chromatography and multi-angle light scattering, we showed that α-catenin and β-catenin formed a heterodimer that bound N. vectensis Cadherin-1 and -2. Nematostella vectensis α-catenin bound F-actin with equivalent affinity as either a monomer or an α/β-catenin heterodimer, and its affinity for F-actin was, in part, regulated by a novel insert between the N- and C-terminal domains. Nematostella vectensis α-catenin inhibited Arp2/3 complex-mediated nucleation of actin filaments, a regulatory property previously thought to be unique to mammalian αE-catenin. Thus, despite significant differences in sequence, the key interactions of the CCC are conserved between bilaterians and cnidarians, indicating that the core function of the CCC as a link between cell adhesions and the actin cytoskeleton is ancestral in the eumetazoans.

    View details for DOI 10.1093/molbev/msw084

    View details for Web of Science ID 000380105900011

    View details for PubMedID 27189570

    View details for PubMedCentralID PMC4948710

  • The deuterostome context of chordate origins NATURE Lowe, C. J., Clarke, D. N., Medeiros, D. M., Rokhsar, D. S., Gerhart, J. 2015; 520 (7548): 456-465

    Abstract

    Our understanding of vertebrate origins is powerfully informed by comparative morphology, embryology and genomics of chordates, hemichordates and echinoderms, which together make up the deuterostome clade. Striking body-plan differences among these phyla have historically hindered the identification of ancestral morphological features, but recent progress in molecular genetics and embryology has revealed deep similarities in body-axis formation and organization across deuterostomes, at stages before morphological differences develop. These developmental genetic features, along with robust support of pharyngeal gill slits as a shared deuterostome character, provide the foundation for the emergence of chordates.

    View details for DOI 10.1038/nature14434

    View details for Web of Science ID 000353334500029

    View details for PubMedID 25903627

  • Germ Cell Specification Requires Zygotic Mechanisms Rather Than Germ Plasm in a Basally Branching Insect CURRENT BIOLOGY Ewen-Campen, B., Donoughe, S., Clarke, D. N., Extavour, C. G. 2013; 23 (10): 835-842

    Abstract

    Primordial germ cell (PGC) specification is a universal process across animals, but the molecular mechanisms specifying PGCs are remarkably diverse. In Drosophila, PGCs are specified by maternally provided, asymmetrically localized cytoplasmic factors (germ plasm). In contrast, historical literature on most other arthropods reports that PGCs arise from mesoderm during midembryogenesis, suggesting that an arthropod last common ancestor may have specified PGCs via zygotic mechanisms. However, there has been no direct experimental evidence to date for germ plasm-independent arthropod PGC specification.Here we show that in a basally branching insect, the cricket Gryllus bimaculatus, conserved germ plasm molecules are ubiquitously, rather than asymmetrically, localized during oogenesis and early embryogenesis. Molecular and cytological analyses suggest that Gryllus PGCs arise from abdominal mesoderm during segmentation, and twist RNAi embryos that lack mesoderm fail to form PGCs. Using RNA interference we show that vasa and piwi are not required maternally or zygotically for PGC formation but rather are required for primary spermatogonial divisions in adult males.These observations suggest that Gryllus lacks a maternally inherited germ plasm, in contrast with many holometabolous insects, including Drosophila. The mesodermal origin of Gryllus PGCs and absence of instructive roles for vasa and piwi in PGC formation are reminiscent of mouse PGC specification and suggest that zygotic cell signaling may direct PGC specification in Gryllus and other Hemimetabola.

    View details for DOI 10.1016/j.cub.2013.03.063

    View details for Web of Science ID 000319482900017

    View details for PubMedID 23623552

  • The evolutionary origin of epithelial cell-cell adhesion mechanisms. Current topics in membranes Miller, P. W., Clarke, D. N., Weis, W. I., Lowe, C. J., Nelson, W. J. 2013; 72: 267-311

    Abstract

    A simple epithelium forms a barrier between the outside and the inside of an organism, and is the first organized multicellular tissue found in evolution. We examine the relationship between the evolution of epithelia and specialized cell-cell adhesion proteins comprising the classical cadherin/β-catenin/α-catenin complex (CCC). A review of the divergent functional properties of the CCC in metazoans and non-metazoans, and an updated phylogenetic coverage of the CCC using recent genomic data reveal: (1) The core CCC likely originated before the last common ancestor of unikonts and their closest bikont sister taxa. (2) Formation of the CCC may have constrained sequence evolution of the classical cadherin cytoplasmic domain and β-catenin in metazoa. (3) The α-catenin-binding domain in β-catenin appears to be the favored mutation site for disrupting β-catenin function in the CCC. (4) The ancestral function of the α/β-catenin heterodimer appears to be an actin-binding module. In some metazoan groups, more complex functions of α-catenin were gained by sequence divergence in the non-actin-binding (N-, M-) domains. (5) Allosteric regulation of α-catenin may have evolved for more complex regulation of the actin cytoskeleton.

    View details for DOI 10.1016/B978-0-12-417027-8.00008-8

    View details for PubMedID 24210433

    View details for PubMedCentralID PMC4118598

  • Effects of night-time warming on temperate ectotherm reproduction: potential fitness benefits of climate change for side-blotched lizards JOURNAL OF EXPERIMENTAL BIOLOGY Clarke, D. N., Zani, P. A. 2012; 215 (7): 1117-1127

    Abstract

    Temperate ectotherms, especially those at higher latitudes, are expected to benefit from climate warming, but few data yet exist to verify this prediction. Furthermore, most previous studies on the effects of climate change utilized a model of uniform annual change, which assumes that temperature increases are symmetric on diurnal or seasonal time scales. In this study, we simulated observed trends in the asymmetric alteration of diurnal temperature range by increasing night-time temperatures experienced by female lizards during their ovarian cycle as well as by the resulting eggs during their incubation. We found that higher night-time temperatures during the ovarian cycle increased the probability of reproductive success and decreased the duration of the reproductive cycle, but did not affect embryo stage or size at oviposition, clutch size, egg mass or relative clutch mass. Furthermore, higher incubation temperatures increased hatchling size and decreased incubation period but had no effect on incubation success. Subsequent hatchlings were more likely to survive winter if they hatched earlier, though our sample size of hatchlings was relatively small. These findings indicate that higher night-time temperatures mainly affect rate processes and that certain aspects of life history are less directly temperature dependent. As our findings confirm that climate warming is likely to increase the rate of development as well as advance reproductive phenology, we predict that warmer nights during the breeding season will increase reproductive output as well as subsequent survival in many temperate ectotherms, both of which should have positive fitness effects.

    View details for DOI 10.1242/jeb065359

    View details for Web of Science ID 000301299500017

    View details for PubMedID 22399656