title: LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors.
abstract: Smooth muscle cell (SMC) plasticity maintains the balance between differentiated SMCs and proliferative mesenchymal progenitors, crucial for muscular tissue homeostasis. Studies on the development of mesenchymal progenitors into SMCs have proven useful in identifying molecular mechanisms involved in digestive musculature plasticity in physiological and pathological conditions.
  
  
  
  Here, we show that Limb Expression 1 (LIX1) molecularly defines the population of mesenchymal progenitors in the developing stomach. Using in vivo functional approaches in the chick embryo, we demonstrate that LIX1 is a key regulator of stomach SMC development. We show that LIX1 is required for stomach SMC determination to regulate the expression of the pro-proliferative gene YAP1 and mesenchymal cell proliferation. However, as stomach development proceeds, sustained LIX1 expression has a negative impact on further SMC differentiation and this is associated with a decrease in YAP1 activity.
  
  
  
  We demonstrate that expression of LIX1 must be tightly regulated to allow fine-tuning of the transcript levels and state of activation of the pro-proliferative transcriptional coactivator YAP1 to regulate proliferation rates of stomach mesenchymal progenitors and their differentiation. Our data highlight dual roles for LIX1 and YAP1 and provide new insights into the regulation of cell density-dependent proliferation, which is essential for the development and homeostasis of organs.
authors.affiliation: PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, 34295, Montpellier, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McKey
authors.affiliation: PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, 34295, Montpellier, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Martire
authors.affiliation: PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, 34295, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: de Santa Barbara
authors.affiliation: PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, 34295, Montpellier, France. sandrine.faure@inserm.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faure
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002642:Chick Embryo; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005819:Genetic Markers; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013270:Stomach / Q000166:cytology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005819:Genetic Markers; D010750:Phosphoproteins; D016601:RNA-Binding Proteins
keywords: Density-dependent cell proliferation; FGF pathway; Gastrointestinal tract; LIX1; Mesenchymal progenitors; Smooth muscle cells; YAP1