Neurovascular patterning cues and implications for central and peripheral neurological disease

Gamboa, Nicholas T.; Taussky, Philipp; Park, Min S; Couldwell, William T.; Mahan, Mark A.; Kalani, M. Yashar S.

doi:10.4103/sni.sni_475_16

Cited by 8 publications

(3 citation statements)

References 172 publications

(178 reference statements)

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“…Glial cells also appeared to communicate with the three EC populations and mural cells (Figure 3A), consistent with the phenomenon of neurovascular congruence in the cardiac sympathetic plexus (Stubbs et al, 2009). In support of this, we detected eight ligands highly specific to glial cells (expressed in <5% of other TIP cells) including Dhh (Desert Hedgehog) and Semaphorin genes Sema3b and Sema4f (Figure 3D), involved in both neural and angiogenic development (Gamboa et al, 2017). Thus, these maps suggest the extent, directionality and complexity of interactions between cardiac cell types in homeostasis and injury.…”

Section: Resultssupporting

confidence: 56%

Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury

Farbehi

Patrick

Dorison

et al. 2019

eLife

457

502

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Besides cardiomyocytes (CM), the heart contains numerous interstitial cell types which play key roles in heart repair, regeneration and disease, including fibroblast, vascular and immune cells. However, a comprehensive understanding of this interactive cell community is lacking. We performed single-cell RNA-sequencing of the total non-CM fraction and enriched (Pdgfra-GFP+) fibroblast lineage cells from murine hearts at days 3 and 7 post-sham or myocardial infarction (MI) surgery. Clustering of >30,000 single cells identified >30 populations representing nine cell lineages, including a previously undescribed fibroblast lineage trajectory present in both sham and MI hearts leading to a uniquely activated cell state defined in part by a strong anti-WNT transcriptome signature. We also uncovered novel myofibroblast subtypes expressing either pro-fibrotic or anti-fibrotic signatures. Our data highlight non-linear dynamics in myeloid and fibroblast lineages after cardiac injury, and provide an entry point for deeper analysis of cardiac homeostasis, inflammation, fibrosis, repair and regeneration.

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Section: Resultssupporting

confidence: 56%

Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury

Farbehi

Patrick

Dorison

et al. 2019

eLife

457

502

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“…Worth to mention, the NF-kB-VEGF cascade in AVMs is also stimulated under hypoxia by HIF-1 (Ng et al, 2005). Consistently, VEGF has been reported in patients suffering from recurrent cerebral AVMs (Rothbart et al, 1996) and VEGF receptors (VEGFR1 and VEGFR2), matrix metalloproteinases-MMP9 and ECM proteins like Collagen IV (Rothbart et al, 1996;Pyo et al, 2000;Hashimoto et al, 2003;Gamboa et al, 2017) are further thought to play a primary role in the pathogenesis of AVMs. As Notch signaling plays a critical role in the determining the arterio-venous cell fate during vascular development, it is thus crucial in AVMs also (Murphy et al, 2008;ZhuGe et al, 2009;Tetzlaff and Fischer, 2018).…”

Section: Common Molecular Factors In Development and Pathologymentioning

confidence: 73%

“…IL-6, IL-1β, and TNFα also induce NF-kB expression, which further exacerbates VEGF levels (Angelo and Kurzrock, 2007). Moreover, it is possible that this AVM niche itself may contribute to the stimulation of pathological angiogenesis, where the occurrence of focal ischemia leads to a hypoxic environment that in turn leads to angiogenesis by the expression of VEGF and VEGFR1 (Rothbart et al, 1996;Koizumi et al, 2002;Jabbour et al, 2009;Mouchtouris et al, 2015;Gamboa et al, 2017). Worth to mention, the NF-kB-VEGF cascade in AVMs is also stimulated under hypoxia by HIF-1 (Ng et al, 2005).…”

Section: Common Molecular Factors In Development and Pathologymentioning

confidence: 99%

Cellular and Molecular Mechanisms of Spinal Cord Vascularization

2020

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During embryonic central nervous system (CNS) development, the neural and the vascular systems communicate with each other in order to give rise to a fully functional and mature CNS. The initial avascular CNS becomes vascularized by blood vessel sprouting from different vascular plexus in a highly stereotypical and controlled manner. This process is similar across different regions of the CNS. In particular for the developing spinal cord (SC), blood vessel ingression occurs from a perineural vascular plexus during embryonic development. In this review, we provide an updated and comprehensive description of the cellular and molecular mechanisms behind this stereotypical and controlled patterning of blood vessels in the developing embryonic SC, identified using different animal models. We discuss how signals derived from neural progenitors and differentiated neurons guide the SC growing vasculature. Lastly, we provide a perspective of how the molecular mechanisms identified during development could be used to better understand pathological situations.

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Diverse roles for axon guidance pathways in adult tissue architecture and function

Laws

Bashaw

2022

Natural Sciences

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Classical axon guidance ligands and their neuronal receptors were first identified due to their fundamental roles in regulating connectivity in the developing nervous system. Since their initial discovery, it has become clear that these signaling molecules play important roles in the development of a broad array of tissue and organ systems across phylogeny. In addition to these diverse developmental roles, there is a growing appreciation that guidance signaling pathways have important functions in adult organisms, including the regulation of tissue integrity and homeostasis. These roles in adult organisms include both tissue‐intrinsic activities of guidance molecules, as well as systemic effects on tissue maintenance and function mediated by the nervous and vascular systems. While many of these adult functions depend on mechanisms that mirror developmental activities, such as regulating adhesion and cell motility, there are also examples of adult roles that may reflect signaling activities that are distinct from known developmental mechanisms, including the contributions of guidance signaling pathways to lineage commitment in the intestinal epithelium and bone remodeling in vertebrates. In this review, we highlight studies of guidance receptors and their ligands in adult tissues outside of the nervous system, focusing on in vivo experimental contexts. Together, these studies lay the groundwork for future investigation into the conserved and tissue‐specific mechanisms of guidance receptor signaling in adult tissues. Key Points Axon guidance ligand and receptor expression often persist into adulthood in neuronal and non‐neuronal tissues alike. Recent work in genetic model organisms highlights the diverse roles of guidance factors in adult tissues. Guidance factors are required intrinsically in a variety of adult tissues but can also regulate tissue function indirectly via functions in the nervous and vascular systems. Studies outside of the nervous system are likely to enhance our understanding of these diverse siganling molecules and could suggest novel signaling modalities in the nervous system.

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Neurovascular patterning cues and implications for central and peripheral neurological disease

Cited by 8 publications

References 172 publications

Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury

Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury

Cellular and Molecular Mechanisms of Spinal Cord Vascularization

Diverse roles for axon guidance pathways in adult tissue architecture and function

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