Biology of vascular mural cells

Siekmann, Arndt F.

doi:10.1242/dev.200271

Cited by 4 publications

(3 citation statements)

References 178 publications

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“…Despite the importance of maintaining vascular hierarchy, the underlying cellular and molecular mechanisms that spatiotemporally establish blood vessel diameters have remained unclear. Mural cellswith their plethora of cell types in differing vascular localizationsare known to regulate blood vessel dilation and constriction in response to shear stress (Siekmann, 2023). However, mural cells do not mature until later in development, and in the zebrafish axial vasculature this occurs at around 3 dpf (Ando et al, 2021(Ando et al, , 2019.…”

Section: Discussionmentioning

confidence: 99%

Alk1/Endoglin dependent increases in vein endothelial cell sizes precipitate arteriovenous malformations

Diwan,

Siekmann

2023

Preprint

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Aberrations in blood vessel diameters can disrupt the hierarchical patterning of the vasculature and cause congenital vascular anomalies, such as arteriovenous malformations (AVMs). Despite the identification of the Bone Morphogenetic Protein (BMP) pathway as a major driver in AVM pathology, we still lack an understanding of the early embryonic events regulating vessel hierarchy and arteriovenous shunt formationin vivo. We therefore studied blood vessel diameter control of the dorsal aorta (DA) and posterior cardinal vein (PCV) in zebrafish embryos. Our findings reveal that increases in blood flow during embryonic development result in increases in arterial endothelial cell (EC) sizes, ultimately enlarging DA diameters. By contrast, anterior regions of the PCV did not respond to changes in blood flow, while caudal regions, close to the artery-vein junction, responded to changes in flow like the DA, but to a lesser extent. To unravel the mechanisms underlying the reduced response of PCV ECs to flow, we studied zebrafish embryos mutant for the BMP pathway componentsendoglinandalk1. Through the generation of genetic mosaics, we discovered that both Endoglin and Alk1 were required cell autonomously in PCV cells to restrict EC sizes and thereby limit venous diameter increases in response to flow. We further revealed that initial increases in the diameter of the caudal PCV secondarily led to increased DA diameters and cell sizes. Therefore, Alk1/Endoglin signaling prevents vein ECs from behaving like arterial ECs. This differential response of arterial and venous EC cells to increases in flow is necessary to prevent the development of AVMs. This study thus offers insights into the spatiotemporal regulation of vessel hierarchy during early development and identifies changes in EC shapes as an important contributor in determining blood vessel diameters. Failure in this mechanism underlies the vein-specific initiation of AVMs in vertebrate models of HHT.

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Section: Discussionmentioning

confidence: 99%

Alk1/Endoglin dependent increases in vein endothelial cell sizes precipitate arteriovenous malformations

Diwan,

Siekmann

2023

Preprint

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“…Regarding the cells of the vasculature in the developing neocortex, there are two major classes: (i) endothelial cells and (ii) mural cells (pericytes and smooth muscle cells) ( Gerhardt and Betsholtz, 2003 ; Daneman et al, 2010 ; Bjornsson et al, 2015 ; Vanlandewijck et al, 2018 ; Siekmann, 2023 ). Endothelial tip cells (ETCs) are a distinct subtype of endothelial cells ( Gerhardt et al, 2003 ; De Smet et al, 2009 ; Eilken and Adams, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, it has been shown that endothelial cells can influence, in co-cultures, progenitor self-renewal and expansion ( Shen et al, 2004 ). Moreover, endothelial cell stabilization and vessel sprouting are influenced by mural cells (summarized in Siekmann (2023) ). In addition, endothelial cell cultures or conditioned medium can modulate the number of neurite outgrowth and spines in maturing neurons ( Wu et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

High-resolution 3D ultrastructural analysis of developing mouse neocortex reveals long slender processes of endothelial cells that enter neural cells

Wilsch-Bräuninger,

Peters,

Huttner

2024

Front. Cell Dev. Biol.

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The development of the neocortex involves an interplay between neural cells and the vasculature. However, little is known about this interplay at the ultrastructural level. To gain a 3D insight into the ultrastructure of the developing neocortex, we have analyzed the embryonic mouse neocortex by serial block-face scanning electron microscopy (SBF-SEM). In this study, we report a first set of findings that focus on the interaction of blood vessels, notably endothelial tip cells (ETCs), and the neural cells in this tissue. A key observation was that the processes of ETCs, located either in the ventricular zone (VZ) or subventricular zone (SVZ)/intermediate zone (IZ), can enter, traverse the cytoplasm, and even exit via deep plasma membrane invaginations of the host cells, including apical progenitors (APs), basal progenitors (BPs), and newborn neurons. More than half of the ETC processes were found to enter the neural cells. Striking examples of this ETC process “invasion” were (i) protrusions of apical progenitors or newborn basal progenitors into the ventricular lumen that contained an ETC process inside and (ii) ETC process-containing protrusions of neurons that penetrated other neurons. Our observations reveal a — so far unknown — complexity of the ETC–neural cell interaction.

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