Epicardium-derived cells (EPDCs) contribute cardiovascular cell types during development and in adulthood respond to Thymosin β4 (Tβ4) and myocardial infarction (MI) by reactivating a fetal gene programme to promote neovascularization and cardiomyogenesis. The mechanism for epicardial gene (re-)activation remains elusive. Here we reveal that BRG1, the essential ATPase subunit of the SWI/SNF chromatin–remodelling complex, is required for expression of Wilms’ tumour 1 (Wt1), fetal EPDC activation and subsequent differentiation into coronary smooth muscle, and restores Wt1 activity upon MI. BRG1 physically interacts with Tβ4 and is recruited by CCAAT/enhancer-binding protein β (C/EBPβ) to discrete regulatory elements in the Wt1 locus. BRG1-Tβ4 co-operative binding promotes optimal transcription of Wt1 as the master regulator of embryonic EPDCs. Moreover, chromatin immunoprecipitation-sequencing reveals BRG1 binding at further key loci suggesting SWI/SNF activity across the fetal epicardial gene programme. These findings reveal essential functions for chromatin–remodelling in the activation of EPDCs during cardiovascular development and repair.

Centrioles are composed of a central cartwheel tethered to nine-fold symmetric microtubule (MT) blades. The centriole cartwheel and MTs are thought to grow from opposite ends of these organelles, so it is unclear how they coordinate their assembly. We previously showed that an oscillation of Polo-like kinase 4 (Plk4) helps to initiate and time the growth of the cartwheel at the proximal end. Here, we show that CP110 and Cep97 form a complex close to the distal-end of the centriole MTs whose levels rise and fall as the new centriole MTs grow, in a manner that appears to be entrained by the core Cdk/Cyclin oscillator that drives the nuclear divisions in these embryos. These CP110/Cep97 dynamics, however, do not appear to time the period of centriole MT growth directly. Instead, we find that changing the levels of CP110/Cep97 appears to alter the Plk4 oscillation and the growth of the cartwheel at the proximal end. These findings reveal an unexpected potential crosstalk between factors normally concentrated at opposite ends of the growing centrioles, which may help to coordinate centriole growth.

SummaryCentrioles are composed of a central cartwheel tethered to nine-fold symmetric microtubule (MT) blades. The centriole cartwheel and MTs are thought to grow from opposite ends of these organelles, so it is unclear how they coordinate their assembly. We previously showed that an oscillation of Polo-like kinase 4 (Plk4) initiates and times the growth of the cartwheel at the proximal end. Here, we show that CP110 and Cep97 form a complex close to the distal-end of the centriole MTs whose levels oscillate as the new centriole MTs grow. The CP110/Cep97 oscillation does not appear to time the period of centriole MT growth, but rather the oscillation is entrained by the core Cdk/Cyclin oscillator that drives the nuclear divisions in these embryos. We find that changing the levels of CP110/Cep97 alters the Plk4 oscillation and the growth of the cartwheel at the proximal end. These findings reveal an unexpected crosstalk between factors normally concentrated at opposite ends of the growing centrioles, which may help to coordinate centriole growth.

Journal of Experimental Biology was launched in 1923 as The British Journal of Experimental Biology, with a single issue being published in the October of that year. As we celebrate our centenary, we look back at that first issue and the zoologists publishing their work in the new journal, and draw comparisons to the JEB that we know today. Much has changed since the publication of the first issue of JEB, in the worlds of both science and publishing, and we eagerly anticipate the next 100 years of discovery.

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