MSGID: 1:317/3 640c03ef   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    How to assemble a complete jaw    
      
     Date:   
         March 10, 2023   
     Source:   
         Keck School of Medicine of USC   
     Summary:   
         The skeleton, tendons, and glands of a functional jaw all derive   
         from the same population of stem cells, which arise from a cell   
         population known as neural crest. To discover how these neural   
         crest-derived cells know to make the right type of cell in the right   
         location, researchers focused on a particular gene, Nr5a2, that   
         was active in a region of the face that makes tendons and glands,   
         but not skeleton. To understand the role of Nr5a2, the scientists   
         created zebrafish lacking this gene. These mutant zebrafish   
         generated excess cartilage and were missing tendons in their jaws.   
      
      
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   FULL STORY   
   ==========================================================================   
   The skeleton, tendons, and glands of a functional jaw all derive from   
   the same population of stem cells, which arise from a cell population   
   known as neural crest. To discover how these neural crest-derived cells   
   know to make the right type of cell in the right location, researchers   
   focused on a particular gene, Nr5a2, that was active in a region of the   
   face that makes tendons and glands, but not skeleton. To understand the   
   role of Nr5a2, the scientists created zebrafish lacking this gene. These   
   mutant zebrafish generated excess cartilage and were missing tendons in   
   their jaws. The scientists then examined the structure of the genome in   
   zebrafish lacking Nr5a2. They found that Nr5a2 was essential for opening   
   up regions of the genome that enable neural crest cells to maintain their   
   stem cell features, while at the same time priming these cells to form   
   tendons and salivary glands later in jaw development.   
      
      
   ==========================================================================   
   A USC-led team of scientists has made a drool-worthy discovery about   
   how tendons and salivary glands develop in the jaw. Their results are   
   published in a new study in Developmental Cell.   
      
   In order for our jaws to function, they require not only a precisely   
   patterned skeleton, but also tendons that connect the jaw skeleton   
   to muscles and salivary glands that lubricate the mouth. Remarkably,   
   the skeleton, tendons, and glands all derive from the same population of   
   stem cells, which arise from a cell population known as neural crest. How   
   these neural crest-derived cells know to make the right type of cell in   
   the right location has remained a mystery.   
      
   To begin answering this question, first author Hung-Jhen (Olivia)   
   Chen from the lab of corresponding author Gage Crump, professor and   
   vice-chair of stem cell biology and regenerative medicine at the Keck   
   School of Medicine of USC, and colleagues examined all the genes that   
   were active in the developing face of zebrafish. They then honed in on   
   one particular gene, Nr5a2, that was active in a region of the face that   
   makes tendons and glands, but not skeleton.   
      
   To understand the role of Nr5a2, the scientists created zebrafish lacking   
   this gene. These mutant zebrafish generated excess cartilage and were   
   missing tendons in their jaws.   
      
   The scientists also developed mice lacking this gene specifically in their   
   neural crest cells. These mice not only had skeletal and tendon defects in   
   their jaws, but also failed to develop salivary glands. Similar defects   
   were also seen in the middle ear, reflecting a dramatic evolutionary   
   transition in which part of the fish jaw became the mammalian middle ear.   
      
   To clarify how this was happening, the scientists examined the structure   
   of the genome in zebrafish lacking Nr5a2. They found that Nr5a2 was   
   essential for opening up regions of the genome that enable neural crest   
   cells to maintain their stem cell features, while at the same time priming   
   these cells to form tendons and salivary glands later in jaw development.   
      
   "Discovery of a very specific role of Nr5a2 in jaw patterning was   
   unexpected, as this gene had previously been shown to be essential for   
   maintaining embryonic stem cells," said Crump. "Our work shows how a key   
   stem cell factor can be used in a different way later in development to   
   control how diverse cell types are made."  Additional co-authors include   
   Lindsey Barske, who completed her postdoctoral training at USC and is   
   now a faculty member at Cincinnati Children's Hospital Medical Center;   
   Jared Talbot from the University of Maine; Olivia Dinwoodie and Abigail   
   Tucker from King's College London; Ryan Roberts, Christian Jimenez, and   
   Amy Merrill from USC; and D'Juan Farmer who completed his postdoctoral   
   training at USC and is now a faculty member at UCLA.   
      
   Funding for this research was provided by the National Institute of Dental   
   Craniofacial Research (grants R21DE029656 and R35DE027550), the Howard   
   Hughes Medical Institute's Hannah H. Gray Fellows Program, and the King's   
   College London Medical Research Council Doctoral Training Partnership.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Stem_Cells # Medical_Topics # Lymphoma # Prostate_Cancer   
             o Plants_&_Animals   
                   # Developmental_Biology # Biotechnology #   
                   Molecular_Biology # Biology   
       * RELATED_TERMS   
             o Human_skeleton o Gene_therapy o Stem_cell o Embryo o   
             Adult_stem_cell o Stem_cell_treatments o Tendon o Somatic_cell   
      
   ==========================================================================   
   Story Source: Materials provided by   
   Keck_School_of_Medicine_of_USC. Original written by Cristy Lytal. Note:   
   Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Hung-Jhen Chen, Lindsey Barske, Jared C. Talbot, Olivia   
      M. Dinwoodie,   
         Ryan R. Roberts, D'Juan T. Farmer, Christian Jimenez, Amy   
         E. Merrill, Abigail S. Tucker, J. Gage Crump. Nuclear receptor Nr5a2   
         promotes diverse connective tissue fates in the jaw. Developmental   
         Cell, 2023; DOI: 10.1016/j.devcel.2023.02.011   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/03/230310123924.htm   
      
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