PMID- 37002923 OWN - NLM STAT- MEDLINE DCOM- 20231004 LR - 20231005 IS - 2211-1247 (Electronic) VI - 42 IP - 4 DP - 2023 Apr 25 TI - Hic1 identifies a specialized mesenchymal progenitor population in the embryonic limb responsible for bone superstructure formation. PG - 112325 LID - S2211-1247(23)00336-4 [pii] LID - 10.1016/j.celrep.2023.112325 [doi] AB - The musculoskeletal system relies on the integration of multiple components with diverse physical properties, such as striated muscle, tendon, and bone, that enable locomotion and structural stability. This relies on the emergence of specialized, but poorly characterized, interfaces between these various elements during embryonic development. Within the appendicular skeleton, we show that a subset of mesenchymal progenitors (MPs), identified by Hic1, do not contribute to the primary cartilaginous anlagen but represent the MP population, whose progeny directly contribute to the interfaces that connect bone to tendon (entheses), tendon to muscle (myotendinous junctions), and the associated superstructures. Furthermore, deletion of Hic1 leads to skeletal defects reflective of deficient muscle-bone coupling and, consequently, perturbation of ambulation. Collectively, these findings show that Hic1 identifies a unique MP population that contributes to a secondary wave of bone sculpting critical to skeletal morphogenesis. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Arostegui, Martin AU - Arostegui M AD - Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. FAU - Scott, R Wilder AU - Scott RW AD - Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada. FAU - Underhill, T Michael AU - Underhill TM AD - Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; School of Biomedical Engineering, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address: tunderhi@brc.ubc.ca. LA - eng GR - MOP-10684/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230331 PL - United States TA - Cell Rep JT - Cell reports JID - 101573691 SB - IM MH - *Tendons MH - *Muscle, Skeletal MH - Osteogenesis MH - Bone and Bones MH - Cartilage OTO - NOTNLM OT - CP: Developmental biology OT - chondrogenesis OT - congenital limb defects OT - enthesis OT - limb development OT - lineage tracing OT - mesenchymal progenitors OT - myotendinous junction OT - single-cell omics OT - skeletal development OT - transgenic models COIS- Declaration of interests The authors declare no competing interests. EDAT- 2023/04/02 06:00 MHDA- 2023/10/04 06:43 CRDT- 2023/04/01 12:36 PHST- 2022/08/10 00:00 [received] PHST- 2022/12/21 00:00 [revised] PHST- 2023/03/17 00:00 [accepted] PHST- 2023/10/04 06:43 [medline] PHST- 2023/04/02 06:00 [pubmed] PHST- 2023/04/01 12:36 [entrez] AID - S2211-1247(23)00336-4 [pii] AID - 10.1016/j.celrep.2023.112325 [doi] PST - ppublish SO - Cell Rep. 2023 Apr 25;42(4):112325. doi: 10.1016/j.celrep.2023.112325. Epub 2023 Mar 31.