Academic Appointments

Boards, Advisory Committees, Professional Organizations

  • Chair, Division of Evolutionary Developmental Biology, Society of Integrative and Comparative Biology (2012 - Present)

Professional Education

  • BSc. Hons, University of Sussex, Biology with European Studies (1991)
  • PhD, Dept of Ecology and Evolution, SUNY Stony Brook, Ecology and Evolution (1998)

Current Research and Scholarly Interests

Evolution and development, specifically the evolution of the deuterostomes

2015-16 Courses

Stanford Advisees

All Publications

  • 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


    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

  • Reconstructing SALMFamide Neuropeptide Precursor Evolution in the Phylum Echinodermata: Ophiuroid and Crinoid Sequence Data Provide New Insights. Frontiers in endocrinology Elphick, M. R., Semmens, D. C., Blowes, L. M., Levine, J., Lowe, C. J., Arnone, M. I., Clark, M. S. 2015; 6: 2-?


    The SALMFamides are a family of neuropeptides that act as muscle relaxants in echinoderms. Analysis of genome/transcriptome sequence data from the sea urchin Strongylocentrotus purpuratus (Echinoidea), the sea cucumber Apostichopus japonicus (Holothuroidea), and the starfish Patiria miniata (Asteroidea) reveals that in each species there are two types of SALMFamide precursor: an L-type precursor comprising peptides with a C-terminal LxFamide-type motif and an F-type precursor solely or largely comprising peptides with a C-terminal FxFamide-type motif. Here, we have identified transcripts encoding SALMFamide precursors in the brittle star Ophionotus victoriae (Ophiuroidea) and the feather star Antedon mediterranea (Crinoidea). We have also identified SALMFamide precursors in other species belonging to each of the five echinoderm classes. As in S. purpuratus, A. japonicus, and P. miniata, in O. victoriae there is one L-type precursor and one F-type precursor. However, in A. mediterranea only a single SALMFamide precursor was found, comprising two peptides with a LxFamide-type motif, one with a FxFamide-type motif, five with a FxLamide-type motif, and four with a LxLamide-type motif. As crinoids are basal to the Echinozoa (Holothuroidea + Echinoidea) and Asterozoa (Asteroidea + Ophiuroidea) in echinoderm phylogeny, one model of SALMFamide precursor evolution would be that ancestrally there was a single SALMFamide gene encoding a variety of SALMFamides (as in crinoids), which duplicated in a common ancestor of the Echinozoa and Asterozoa and then specialized to encode L-type SALMFamides or F-type SALMFamides. Alternatively, a second SALMFamide precursor may remain to be discovered or may have been lost in crinoids. Further insights will be obtained if SALMFamide receptors are identified, which would provide a molecular basis for experimental analysis of the functional significance of the "cocktails" of SALMFamides that exist in echinoderms.

    View details for DOI 10.3389/fendo.2015.00002

    View details for PubMedID 25699014

  • On a Possible Evolutionary Link of the Stomochord of Hemichordates to Pharyngeal Organs of Chordates GENESIS Satoh, N., Tagawa, K., Lowe, C. J., Yu, J., Kawashima, T., Takahashi, H., Ogasawara, M., Kirschner, M., Hisata, K., Su, Y., Gerhart, J. 2014; 52 (12): 925-934


    As a group closely related to chordates, hemichordate acorn worms are in a key phylogenic position for addressing hypotheses of chordate origins. The stomochord of acorn worms is an anterior outgrowth of the pharynx endoderm into the proboscis. In 1886 Bateson proposed homology of this organ to the chordate notochord, crowning this animal group "hemichordates." Although this proposal has been debated for over a century, the question still remains unresolved. Here we review recent progress related to this question. First, the developmental mode of the stomochord completely differs from that of the notochord. Second, comparison of expression profiles of genes including Brachyury, a key regulator of notochord formation in chordates, does not support the stomochord/notochord homology. Third, FoxE that is expressed in the stomochord-forming region in acorn worm juveniles is expressed in the club-shaped gland and in the endostyle of amphioxus, in the endostyle of ascidians, and in the thyroid gland of vertebrates. Based on these findings, together with the anterior endodermal location of the stomochord, we propose that the stomochord has evolutionary relatedness to chordate organs deriving from the anterior pharynx rather than to the notochord.

    View details for DOI 10.1002/dvg.22831

    View details for Web of Science ID 000346702100001

    View details for PubMedID 25303744

  • Animal evolution: stiff or squishy notochord origins? Current biology Hejnol, A., Lowe, C. J. 2014; 24 (23): R1131-3


    The notochord is considered an evolutionary novelty and one of the defining characters of chordates. A new study of an annelid challenges this view and proposes an earlier evolutionary origin in the most recent common ancestor of chordates and annelids.

    View details for DOI 10.1016/j.cub.2014.10.059

    View details for PubMedID 25465334

  • Phylogenomic analysis of echinoderm class relationships supports Asterozoa PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Telford, M. J., Lowe, C. J., Cameron, C. B., Ortega-Martinez, O., Aronowicz, J., Oliveri, P., Copley, R. R. 2014; 281 (1786)
  • The Fox/Forkhead transcription factor family of the hemichordate Saccoglossus kowalevskii EVODEVO Fritzenwanker, J. H., Gerhart, J., Freeman, R. M., Lowe, C. J. 2014; 5
  • The Fox/Forkhead transcription factor family of the hemichordate Saccoglossus kowalevskii. EvoDevo Fritzenwanker, J. H., Gerhart, J., Freeman, R. M., Lowe, C. J. 2014; 5: 17-?


    The Fox gene family is a large family of transcription factors that arose early in organismal evolution dating back to at least the common ancestor of metazoans and fungi. They are key components of many gene regulatory networks essential for embryonic development. Although much is known about the role of Fox genes during vertebrate development, comprehensive comparative studies outside vertebrates are sparse. We have characterized the Fox transcription factor gene family from the genome of the enteropneust hemichordate Saccoglossus kowalevskii, including phylogenetic analysis, genomic organization, and expression analysis during early development. Hemichordates are a sister group to echinoderms, closely related to chordates and are a key group for tracing the evolution of gene regulatory mechanisms likely to have been important in the diversification of the deuterostome phyla.Of the 22 Fox gene families that were likely present in the last common ancestor of all deuterostomes, S. kowalevskii has a single ortholog of each group except FoxH, which we were unable to detect, and FoxQ2, which has three paralogs. A phylogenetic analysis of the FoxQ2 family identified an ancestral duplication in the FoxQ2 lineage at the base of the bilaterians. The expression analyses of all 23 Fox genes of S. kowalevskii provide insights into the evolution of components of the regulatory networks for the development of pharyngeal gill slits (foxC, foxL1, and foxI), mesoderm patterning (foxD, foxF, foxG), hindgut development (foxD, foxI), cilia formation (foxJ1), and patterning of the embryonic apical territory (foxQ2).Comparisons of our results with data from echinoderms, chordates, and other bilaterians help to develop hypotheses about the developmental roles of Fox genes that likely characterized ancestral deuterostomes and bilaterians, and more recent clade-specific innovations.

    View details for DOI 10.1186/2041-9139-5-17

    View details for PubMedID 24987514

  • FGF signaling induces mesoderm in the hemichordate Saccoglossus kowalevskii DEVELOPMENT Green, S. A., Norris, R. P., Terasaki, M., Lowe, C. J. 2013; 140 (5): 1024-1033


    FGFs act in vertebrate mesoderm induction and also play key roles in early mesoderm formation in ascidians and amphioxus. However, in sea urchins initial characterizations of FGF function do not support a role in early mesoderm induction, making the ancestral roles of FGF signaling and mechanisms of mesoderm specification in deuterostomes unclear. In order to better characterize the evolution of mesoderm formation, we have examined the role of FGF signaling during mesoderm development in Saccoglossus kowalevskii, an experimentally tractable representative of hemichordates. We report the expression of an FGF ligand, fgf8/17/18, in ectoderm overlying sites of mesoderm specification within the archenteron endomesoderm. Embryological experiments demonstrate that mesoderm induction in the archenteron requires contact with ectoderm, and loss-of-function experiments indicate that both FGF ligand and receptor are necessary for mesoderm specification. fgf8/17/18 gain-of-function experiments establish that FGF8/17/18 is sufficient to induce mesoderm in adjacent endomesoderm. These experiments suggest that FGF signaling is necessary from the earliest stages of mesoderm specification and is required for all mesoderm development. Furthermore, they suggest that the archenteron is competent to form mesoderm or endoderm, and that FGF signaling from the ectoderm defines the location and amount of mesoderm. When considered in a comparative context, these data support a phylogenetically broad requirement for FGF8/17/18 signaling in mesoderm specification and suggest that FGF signaling played an ancestral role in deuterostome mesoderm formation.

    View details for DOI 10.1242/dev.083790

    View details for Web of Science ID 000314879800011

    View details for PubMedID 23344709

  • The Evolutionary Origin of Epithelial Cell-Cell Adhesion Mechanisms FUNCTIONAL ORGANIZATION OF VERTEBRATE PLASMA MEMBRANE Miller, P. W., Clarke, D. N., Weis, W. I., Lowe, C. J., Nelson, W. J. 2013; 72: 267-311


    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 Web of Science ID 000329254600009

  • Identical Genomic Organization of Two Hemichordate Hox Clusters CURRENT BIOLOGY Freeman, R., Ikuta, T., Wu, M., Koyanagi, R., Kawashima, T., Tagawa, K., Humphreys, T., Fang, G., Fujiyama, A., Saiga, H., Lowe, C., Worley, K., Jenkins, J., Schmutz, J., Kirschner, M., Rokhsar, D., Satoh, N., Gerhart, J. 2012; 22 (21): 2053-2058


    Genomic comparisons of chordates, hemichordates, and echinoderms can inform hypotheses for the evolution of these strikingly different phyla from the last common deuterostome ancestor. Because hox genes play pivotal developmental roles in bilaterian animals, we analyzed the Hox complexes of two hemichordate genomes. We find that Saccoglossus kowalevskii and Ptychodera flava both possess 12-gene clusters, with mir10 between hox4 and hox5, in 550 kb and 452 kb intervals, respectively. Genes hox1-hox9/10 of the clusters are in the same genomic order and transcriptional orientation as their orthologs in chordates, with hox1 at the 3' end of the cluster. At the 5' end, each cluster contains three posterior genes specific to Ambulacraria (the hemichordate-echinoderm clade), two forming an inverted terminal pair. In contrast, the echinoderm Strongylocentrotus purpuratus contains a 588 kb cluster of 11 orthologs of the hemichordate genes, ordered differently, plausibly reflecting rearrangements of an ancestral hemichordate-like ambulacrarian cluster. Hox clusters of vertebrates and the basal chordate amphioxus have similar organization to the hemichordate cluster, but with different posterior genes. These results provide genomic evidence for a well-ordered complex in the deuterostome ancestor for the hox1-hox9/10 region, with the number and kind of posterior genes still to be elucidated.

    View details for DOI 10.1016/j.cub.2012.08.052

    View details for Web of Science ID 000311060200028

    View details for PubMedID 23063438

  • Evolutionary crossroads in developmental biology: hemichordates DEVELOPMENT Roettinger, E., Lowe, C. J. 2012; 139 (14): 2463-2475

    View details for DOI 10.1242/dev.066712

    View details for Web of Science ID 000305826000003

  • Ancient deuterostome origins of vertebrate brain signalling centres NATURE Pani, A. M., Mullarkey, E. E., Aronowicz, J., Assimacopoulos, S., Grove, E. A., Lowe, C. J. 2012; 483 (7389): 289-U79


    Neuroectodermal signalling centres induce and pattern many novel vertebrate brain structures but are absent, or divergent, in invertebrate chordates. This has led to the idea that signalling-centre genetic programs were first assembled in stem vertebrates and potentially drove morphological innovations of the brain. However, this scenario presumes that extant cephalochordates accurately represent ancestral chordate characters, which has not been tested using close chordate outgroups. Here we report that genetic programs homologous to three vertebrate signalling centres-the anterior neural ridge, zona limitans intrathalamica and isthmic organizer-are present in the hemichordate Saccoglossus kowalevskii. Fgf8/17/18 (a single gene homologous to vertebrate Fgf8, Fgf17 and Fgf18), sfrp1/5, hh and wnt1 are expressed in vertebrate-like arrangements in hemichordate ectoderm, and homologous genetic mechanisms regulate ectodermal patterning in both animals. We propose that these genetic programs were components of an unexpectedly complex, ancient genetic regulatory scaffold for deuterostome body patterning that degenerated in amphioxus and ascidians, but was retained to pattern divergent structures in hemichordates and vertebrates.

    View details for DOI 10.1038/nature10838

    View details for Web of Science ID 000301481800040

    View details for PubMedID 22422262

  • Animal Evolution: A Soap Opera of Unremarkable Worms CURRENT BIOLOGY Lowe, C. J., Pani, A. M. 2011; 21 (4): R151-R153


    Recent phylogenies have suggested that acoelomorph flatworms might provide insights into the nature of the ancestor of bilaterian animals. However, according to new data acoelomorphs might instead be degenerate deuterostomes closely related to Xenoturbella, muddying the waters of early animal evolution.

    View details for Web of Science ID 000287767600008

    View details for PubMedID 21334293

  • Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Sobreira, T. J., Marletaz, F., Simoes-Costa, M., Schechtman, D., Pereira, A. C., Brunet, F., Sweeney, S., Pani, A., Aronowicz, J., Lowe, C. J., Davidson, B., Laudet, V., Bronner, M., De Oliveira, P. S., Schubert, M., Xavier-Neto, J. 2011; 108 (1): 226-231


    Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification.

    View details for DOI 10.1073/pnas.1011223108

    View details for Web of Science ID 000285915000044

    View details for PubMedID 21169504