LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors

Abstract : AbstractBackgroundSmooth 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.ResultsHere, 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.ConclusionsWe 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.
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Article dans une revue
BMC Biology, BioMed Central, 2015, 14 (1), pp.34. 〈10.1186/s12915-016-0257-2〉
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Soumis le : vendredi 27 mai 2016 - 11:52:05
Dernière modification le : jeudi 5 juillet 2018 - 12:14:03

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Jennifer Mckey, Delphine Martire, Pascal De Santa Barbara, Sandrine Faure. LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors. BMC Biology, BioMed Central, 2015, 14 (1), pp.34. 〈10.1186/s12915-016-0257-2〉. 〈inserm-01322558〉

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