1879-044533132023Jul10Curr BiolSpatial transcriptomics reveals a cnidarian segment polarity program in Nematostella vectensis.26782689.e52678-2689.e510.1016/j.cub.2023.05.044S0960-9822(23)00676-0During early animal evolution, the emergence of axially polarized segments was central to the diversification of complex bilaterian body plans. Nevertheless, precisely how and when segment polarity pathways arose remains obscure. Here, we demonstrate the molecular basis for segment polarization in developing larvae of the sea anemone Nematostella vectensis. Utilizing spatial transcriptomics, we first constructed a 3D gene expression atlas of developing larval segments. Capitalizing on accurate in silico predictions, we identified Lbx and Uncx, conserved homeodomain-containing genes that occupy opposing subsegmental domains under the control of both bone morphogenetic protein (BMP) signaling and the Hox-Gbx cascade. Functionally, Lbx mutagenesis eliminated all molecular evidence of segment polarization at the larval stage and caused an aberrant mirror-symmetric pattern of retractor muscles (RMs) in primary polyps. These results demonstrate the molecular basis for segment polarity in a non-bilaterian animal, suggesting that polarized metameric structures were present in the Cnidaria-Bilateria common ancestor over 600 million years ago.Copyright © 2023 Elsevier Inc. All rights reserved.HeShuonanSStowers Institute for Medical Research, Kansas City, MO 64110, USA.ShaoWanqingWDepartment of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.ChenShiyuan CynthiaSCStowers Institute for Medical Research, Kansas City, MO 64110, USA.WangTingTDepartment of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA; Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.GibsonMatthew CMCStowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Anatomy and Cell Biology, The University of Kansas School of Medicine, Kansas City, KS 66160, USA. Electronic address: mg2@stowers.org.engR01 HG007175HGNHGRI NIH HHSUnited StatesU24 ES026699ESNIEHS NIH HHSUnited StatesU01 CA200060CANCI NIH HHSUnited StatesU01 HG009391HGNHGRI NIH HHSUnited StatesU41 HG010972HGNHGRI NIH HHSUnited StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20230613