{"id":10864,"date":"2025-03-06T16:33:43","date_gmt":"2025-03-07T00:33:43","guid":{"rendered":"https:\/\/grassfoundation.org\/?p=10864"},"modified":"2025-03-06T16:33:43","modified_gmt":"2025-03-07T00:33:43","slug":"first-genome-edited-horseshoe-crabs-guilherme-gainett","status":"publish","type":"post","link":"https:\/\/grassfoundation.org\/?p=10864","title":{"rendered":"First Genome-Edited Horseshoe Crabs"},"content":{"rendered":"<p><span style=\"font-weight: 400;\">We may call them \u201ccrabs,\u201d but horseshoe crabs are more closely related to spiders and scorpions than to the crustaceans they share their coastal homes with. The four species in existence today can be found along the east coasts of North America and South Asia, descendants of creatures found in the fossil record as far back as 445 million years. Sometimes called \u201cliving fossils,\u201d the horseshoe crabs we see today have changed little in the last 250 million years. After all, when it comes to evolution, <\/span><i><span style=\"font-weight: 400;\">if it ain\u2019t broke, don\u2019t fix it.<\/span><\/i><\/p>\n<p><span style=\"font-weight: 400;\">In 1967, Haldan Keffer Hartline won the Nobel Prize in Physiology or Medicine for research on the eyes of horseshoe crabs, but in the decades that followed, the research on these animals\u2019 unique biology slowed down considerably.\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">This has long puzzled <a href=\"https:\/\/grassfoundation.org\/people\/guilherme-gainett\/\" target=\"_blank\" rel=\"noopener\">2024 Grass Fellow Guilherme Gainett<\/a>, a postdoctoral fellow at Boston Children&#8217;s Hospital and Harvard University. As a development biologist, he is fascinated by these ancient creatures and what their eyes can teach us about the evolution of sensory systems. Because while spiders, scorpions and other related arthropods have eyes with a single lens (similar to our human eyes) their ancestors had eyes with multiple lenses, something that you see today in most crustaceans and insects. Today\u2019s horseshoe crabs have <\/span><span style=\"font-weight: 400;\">two lateral compound eyes and two median single-lens eyes, as well as additional photoreceptors, such as those on their telson (tail).<\/span><\/p>\n<p><span style=\"font-weight: 400;\">\u201cHorseshoe crabs are the only animals in this group that includes spiders that retain this ancestral compound eyes,\u201d said Gainett. \u201cSo they&#8217;re really a key lineage for understanding this transition, and I&#8217;m interested in understanding these changes in types of sensory systems.\u201d<\/span><\/p>\n<p><iframe loading=\"lazy\" title=\"YouTube video player\" src=\"\/\/www.youtube.com\/embed\/wBw9jwdAnhQ?si=-cfFdhUtC3T4Bc9I\" width=\"560\" height=\"315\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<p><span style=\"font-weight: 400;\">Gainett set out to the Marine Biological Laboratory to develop new tools for genetic studies in the Atlantic horseshoe crab <\/span><i><span style=\"font-weight: 400;\">L. polyphemus<\/span><\/i><span style=\"font-weight: 400;\">, to help demystify the molecular mechanisms that control their eye development. First he looked at the gene expression across the eyes in embryonic horseshoe crabs, <\/span><span style=\"font-weight: 400;\">noting that some important genes that regulate eye development are expressed in the compound lateral eyes, but not in the single-lens median eyes, suggesting that different upstream regulators initiate their development.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">He also used CRISPR-Cas9 to target the tryptophan 2,3-dioxygenase (TDO) gene, which encodes an enzyme required for pigment formation, resulting in the first genome-edited horseshoe crabs, in this case with clear, whitish eyes.\u00a0<\/span><\/p>\n<div id=\"attachment_10869\" style=\"width: 694px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-10869\" class=\"wp-image-10869 size-full\" src=\"https:\/\/grassfoundation.org\/wp-content\/uploads\/2025\/03\/gui-gainett-horshoe-crabs-crispr.png\" alt=\"A photo of two small horseshoe crab embryos still in the egg. The one on the left has dark eye spots, and the one on the right has clear\/whitish eye spots.\" width=\"684\" height=\"328\" srcset=\"https:\/\/grassfoundation.org\/wp-content\/uploads\/2025\/03\/gui-gainett-horshoe-crabs-crispr.png 684w, https:\/\/grassfoundation.org\/wp-content\/uploads\/2025\/03\/gui-gainett-horshoe-crabs-crispr-300x144.png 300w, https:\/\/grassfoundation.org\/wp-content\/uploads\/2025\/03\/gui-gainett-horshoe-crabs-crispr-600x288.png 600w\" sizes=\"auto, (max-width: 684px) 100vw, 684px\" \/><p id=\"caption-attachment-10869\" class=\"wp-caption-text\">CRISPR-Cas9 genome-editing in the horseshoe crab L. polyphemus. The left shows an unedited control, and the right shows the effect of TDO sgRNA CRISPR-Cas9 treatment, with a noted absence of dark pigment.<\/p><\/div>\n<p><span style=\"font-weight: 400;\">\u201cResearch-wise it was really amazing and transformative for me, describing this very efficient protocol for doing genome-editing in horseshoe crabs,\u201d said Gainett. \u201cIt felt for me as a moment of refreshing my science.\u201d<\/span><\/p>\n<p><span style=\"font-weight: 400;\">The results from Gainett\u2019s summer at the Marine Biological Laboratory open new doors into our understanding of the molecular basis of compound eye development with implications for the evolution of different types of eyes. And equipped with the first-ever protocol for genome-editing in horseshoe crabs, researchers can unlock more secrets hidden in the genomes of these unique creatures.<\/span><\/p>\n<p><span style=\"font-weight: 400;\">Gainett credits his productive summer at MBL to his supportive cohort of 2024 Grass Fellows, the exceptional facilities, mentors such as horseshoe crab expert Dan Gibson, and the enthusiastic surrounding community of researchers.\u00a0\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400;\">\u201cThere&#8217;s definitely some magic that happens there at the MBL,\u201d he said.<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>We may call them \u201ccrabs,\u201d but horseshoe crabs are more closely related to spiders and scorpions than to the crustaceans they share their coastal homes with. The four species in existence today can be found along the east coasts of North America and South Asia, descendants of creatures found in the fossil record as far [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":10867,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[19],"tags":[],"class_list":["post-10864","post","type-post","status-publish","format-standard","hentry","category-news"],"_links":{"self":[{"href":"https:\/\/grassfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/10864","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/grassfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/grassfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/grassfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/grassfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=10864"}],"version-history":[{"count":0,"href":"https:\/\/grassfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/10864\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/grassfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/10867"}],"wp:attachment":[{"href":"https:\/\/grassfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=10864"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/grassfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=10864"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/grassfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=10864"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}