Prox1 maintains muscle structure and growth in the developing heart

Risebro, Catherine A.; Searles, Richelle G.; Melville, Athalie A. D.; Ehler, Elisabeth; Jina, Nipurna; Shah, Sonia; Pallas, Jacqueline A.; Hubank, Mike; Dillard, Miriam E.; Harvey, Natasha L.; Schwartz, Robert J.; Chien, Kenneth R.; Oliver, Guillermo; Riley, Paul R.

doi:10.1242/dev.034264

Cited by 25 publications

(27 citation statements)

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“…Although Prox1 is considered a lymphatic-specific marker [36], its expression has also been reported in various nonlymphatic tissues including liver [69], brain [43], heart [62], pancreas [75], eye [18,71], ear [17], and small intestine [60]. In line with these observations, we detected Prox1 in non-LECs in several normal organs of p50 KO and WT mice, including liver hepatocytes, brain neurons, and heart cardiomyocytes.…”

Section: Nf-jb P50 Also Regulates Prox1 In Some Non-lymphatic Cell Typessupporting

confidence: 82%

“…In addition to hepatocytes, Prox1 has also been detected in several other non-LEC types including cardiomyocytes [62] and neurons [43]. We, therefore, sought to determine whether the absence of p50 in brains and hearts of p50 KO mice causes similar decrease in Prox1 expression as observed in the liver.…”

Section: Expression Of Prox1 Is Decreased In the Brain But Not In Thmentioning

confidence: 99%

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Regulatory Role of the NF-kB Pathway in Lymphangiogenesis and Breast Cancer Metastasis

Flister¹

2010

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Section: Nf-jb P50 Also Regulates Prox1 In Some Non-lymphatic Cell Typessupporting

confidence: 82%

Section: Expression Of Prox1 Is Decreased In the Brain But Not In Thmentioning

confidence: 99%

Regulatory Role of the NF-kB Pathway in Lymphangiogenesis and Breast Cancer Metastasis

Flister¹

2010

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“…Among lymphatic transcriptional regulators, Prox1 has emerged as the master transcription factor responsible for inducing and maintaining LEC identity. Interestingly, Prox1 plays a parallel role in cardiomyocytes, where it regulates cardiac hypertrophic responses 32 , as well as the switch between expression of fast-twitch and slow-twitch muscle genes in heart 33 and skeletal muscle 34 . Indeed, cardiomyocyte-specific Prox1-deficiency in mice leads to overexpression of fast-twitch muscle genes and development of early-onset dilated cardiomyopathy (DCM) 33 .…”

Section: Lymphatic Vasculature: Structure and Function And Remodelingmentioning

confidence: 99%

Cardiac lymphatics in health and disease

2018

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The lymphatic vasculature, which accompanies the blood vasculature in most organs, is indispensable in for maintenance of tissue fluid homeostasis, immune cell trafficking and nutritional lipid uptake and transport, as well as reverse cholesterol transport. In this review, we discuss the physiological role of lymphatics in the heart, in maintenance of cardiac health, and describe alterations of lymphatic structure and function that occur in cardiovascular pathology, including atherosclerosis and myocardial infarction. We further discuss briefly the role that immune cells may play in the regulation of lymphatic growth (lymphangiogenesis) and function. Finally, we provide recent examples of how the cardiac lymphatics may be targeted therapeutically to restore lymphatic drainage in the heart in order to limit myocardial edema and chronic inflammation. Key points  Cardiac lymphatics display a dynamic range of fluid uptake and transport, linked to cardiac contractility and heart rate  Cardiac lymphatics undergo significant remodeling in several cardiovascular diseases, which can alter the lymphatic drainage capacity in the heart  Insufficient lymphangiogenesis may contribute to the buildup of atherosclerotic lesions in large arteries due to accumulation of both lipids and activated immune cells  Immune cells contribute to the process of lymphatic remodeling by stimulating or inhibiting lymphangiogenesis  Therapeutic stimulation of cardiac lymphangiogenesis after myocardial infarction leads to accelerated resolution of myocardial edema and inflammation, promoting cardiac recovery

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“…Prox1 functions as a homeobox transcription regulator. It was shown to be transiently expressed during embryonic development within heart, liver, pancreas, and the CNS, suggesting a role in cell differentiation . With regard to the developing mammalian CNS, Prox1 expression was found in locations where neurogenesis and gliogenesis occurs and where it appears to control cell cycle progression .…”

Section: Introductionmentioning

confidence: 99%

Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone

et al. 2016

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Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thus, our work uncovers a novel function of Prox1 as a fate determinant for oligodendrocytes in the adult mammalian brain. These data indicate that the neurogenic and oligodendrogliogenic lineages in the two adult neurogenic niches exhibit a distinct requirement for Prox1, being important for neurogenesis in the DG but being indispensable for oligodendrogliogenesis in the SVZ. STEM CELLS 2016;34:2115-2129 SIGNIFICANCE STATEMENTIn the submitted study, we address the function of the homeobox transcription factor Prox1 for the specification of oligodendrocyte cell fate in adult neural stem cells. A function of Prox1 for neurogenesis is well described in Drosophila. Additionally, recently its implication in neuronal differentiation in neural stem cells has been shown. Therefore, the function seemed to be totally conserved from Drosophila to mammals. However, we here show that the function of Prox1 depends on the regional identity of the investigated neural stem cells. In neural stem cells of the hippocampus, Prox1 induces neuronal differentiation. However, in neural stem cell from the subventricular zone Prox1 induces differentiation in oligodendrocytes.

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Prox1 maintains muscle structure and growth in the developing heart

Cited by 25 publications

References 0 publications

Regulatory Role of the NF-kB Pathway in Lymphangiogenesis and Breast Cancer Metastasis

Regulatory Role of the NF-kB Pathway in Lymphangiogenesis and Breast Cancer Metastasis

Cardiac lymphatics in health and disease

Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone

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