公募シンポジウム１３：イメージングと形態学から解き明かす神経 －血管作動原理
Symposium13 : Exploring the mechanisms and functions of neurovascular unit using imaging and morphology |
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| 2020/9/12 14:50～15:10 Zoom B
SY13-01
アストロサイト前駆細胞の移動過程と血管との相互作用
Migratory behaviors of astrocyte progenitors and their interactions with blood vessels
*田畑 秀典1
1. 愛知県医療療育総合センター 発達障害研究所
*Hidenori Tabata1
1. Institute for Developmental Research, Aichi Developmental Disability Center
During the development of mammalian cerebral cortex, astrocytes, which eventually become the most abundant cell type in the brains, are produced after the generation of cortical excitatory neurons, and enter the cortical plate, where they actively regulate synaptogenesis as well as formation of blood brain barrier (BBB). To participate in these developmental processes, astrocytes need to settle in the right place at the right time. However, the migratory mechanisms of astrocytes is so far largely unknown. We observed two distinct migration modes of astrocyte progenitors, erratic migration and blood vessel-guided migration. In erratic migration mode, astrocyte progenitors move quickly (maximum speed is over 100 µm) with frequent changes of moving directions, whereas in blood vessel-guided migration, they migrate along the blood vessels toward the pial surface. The blood vessel-guided migration is frequently found especially in the upper cortical plate, where the blood vessels tend to run vertically and provide an appropriate guid for astrocyte progenitors to reach the top of cortical plate. Interestingly, we observed that astrocyte progenitors supported branch formation of blood vessels. In these cases, astrocytes formed a bridge between two adjacent vessels and then endothelial cells extended a process along the bridge and fused to the other side of blood vessel. These observations suggest that the astrocyte migration and the blood vessel network formation are mutually depending. We will discuss the molecular mechanisms for these events and the genetic or environmental factors that can perturb them.
| | 2020/9/12 15:10～15:30 Zoom B
SY13-02
脳室下帯ホールマウントイメージングによる斑点状基底膜の同定と機能解析
Identification and characterization of the speckled basement membranes by whole mount imaging of adult ventricular-subventricular zone
*佐藤 祐哉1
1. 神戸大学大学院医学研究科 神経分化・再生分野
*Yuya Sato1
1. Div. Neural Diff. Regen., Grad. Sch. Med., Kobe Univ.
Neurogenesis persists throughout life in the ventricular-subventricular zone (V-SVZ), where neural stem cells (NSCs) are retained in a specialized neurogenic niche with a unique cellular architecture. Although a variety of cells, including ependymal cells and endothelial cells, are reported to serve as NSC niche, it currently remains unclear whether or how NSCs utilize basement membranes (BMs) in this niche. Here, we examine the molecular compositions and functions of BMs in the adult mouse V-SVZ. By utilizing whole-mount V-SVZ immunostaining and tissue clearing procedure, we found a numerous number of speckled BMs on the surface of V-SVZs. The speckled BMs are produced during postnatal day 5-10, and localized in close proximity to the ependymal cells and NSCs but not to the vascular endothelial cells. A panel of antibodies against BM proteins revealed the difference in molecular composition of the speckled BMs from vascular BMs, supporting to the notion that the speckled BMs are functionally and structurally different from the vascular BMs. Mouse glial fibrillary acidic protein (GFAP) promoter-driven conditional knockout of Lama5 gene revealed that GFAP-positive astrocytes and NSCs produce laminin α5 subunit in the speckled BMs. Furthermore, GFAP-Cre-mediated Lamc1flox(E1605Q) knockin mice, in which integrin-binding activities of laminins are specifically nullified in GFAP-positive cells, exhibit a decreased number and size of speckled BMs and reduced in vitro neurosphere-forming activity. Taken together, our results reveal niche activities of speckled BMs for NSCs and provide molecular insights into how laminin-integrin interactions regulate NSCs in vivo.
| | 2020/9/12 15:30～15:50 Zoom B
SY13-03
血流動態と細胞形態の同時解析を実現する生体マウス最適化ライブイメージング
The Optimization Technology of Intravital Imaging for Living Mice Can Visualize Cell Dynamics in Blood Vessels.
*曽我部 舞奈1
1. 京都大学
*Maina Sogabe1
1. Kyoto University
Live animal imaging is the most commonly used approach to studying living organisms and is used broadly in biological fields to study development, regeneration, and a variety of physiological and biochemical processes.
However, there is room for improvement within intravital volumetric imaging, especially imaging of soft tissues (e.g., blood flow dynamics, inflammatory responses, stem cell proliferation, etc.). For example, increasing imaging duration may lead to many un-modellable artifacts caused by involuntary muscle movement or breathing, and these uncontrollable movements cause cell shape's deformations. Additionally, dynamic biological visualization requires high throughput, time resolution, and spacious field to achieve live imaging.
With current technology, solving these problems is not easy. In this presentation, first, I would like to introduce a new intravital imaging technology that utilizes an information engineering approach. Second, I would talk about practical intravital imaging for blood vessel using the combination of interlaced scan and simple image-replenishment algorithm based on measurement sparsity and graph Laplacian.
Our technique indicates that the proposed method is robust and could be employed for other intravital tissue imaging applications. Furthermore, our findings suggest that the proposed method enables images to be captured at higher vps, which is suitable for volumetric imaging of blood flow.
| | 2020/9/12 15:50～16:10 Zoom B
SY13-04
領域特有の血管網は、固有の微小環境を構築する
Spatiotemporally dependent niche is constructed by the different vascular plexus
*水谷 健一1
1. 神戸学院大学 薬学研究科
*Ken-ichi Mizutani1
1. Graduate School of Pharmaceutical Sciences, Kobe Gakuin University
The blood vessels supply oxygen and nutrients to all the cells in the living body, and provide essential transport routes for collecting waste products. For these functions, blood vessel networks should be appropriately formed in each tissue. The blood vessels have a relatively simple structure consisting of endothelial cells covering the inner layer and pericytes or smooth muscle cells surrounding the outside. However, the structure of vascular network is extremely diverse, with the blood vessels organized depending on tissues to create tissue-specific microenvironments. Recent our study suggested that neocortical angiogenesis develops in a stereotypical spatial pattern during neurogenesis and that vascular/avascular regions are tightly controlled in the developing neocortex to construct a specialized vascular niche that supports ongoing neurogenesis during neocortical development. In this symposium, we will discuss that periventricular blood vessels selectively influence neocortical progenitor behavior and neurogenesis, highlighting how spatiotemporally dependent vascularization with specific morphology is utilized to construct neocortical cytoarchitecture.
| | 2020/9/12 16:10～16:30 Zoom B
SY13-05
神経と血管の相互作用を人為操作する超分子ペプチド材料
Supramolecular peptides manipulating the interaction between nerves and blood vessels
*味岡 逸樹1,2、村岡 貴博3、渡辺 豪4
1. 東京医科歯科大学、2. 神奈川県立産業技術総合研究所、3. 東京農工大学、4. 北里大学
*Itsuki Ajioka1,2, Takahiro Muraoka3, Go Watanabe4
1. Tokyo Medical and Dental University, 2. KISTEC, 3. Tokyo University of Agriculture and Technology, 4. Kitasato University
The extracellular matrix (ECM) is the complex crosslinked network of proteins and other biomolecules and provides a biological niche to regulate the interaction between nerves and blood vessels. A supramolecular peptide hydrogel is widely used in clinical application as an artificial ECM because it degrades into non-toxic peptides. Supramolecular assemblies by the non-covalent association of peptides can mimic such a ECM niche. Using ionic and hydrophobic interactions of amino acid side chain, oligopeptides self-assemble in an antiparallel manner and form nanofibers. These oligopeptides form hydrogels and enhance cell adhesion.
Ischemic brain stroke is caused by blood flow interruption, leading to focal ischemia, neuron death, and motor, sensory, and/or cognitive dysfunctions. Angiogenesis, neovascularization from existing blood vessel, is essential for tissue growth and repair. Proangiogenic therapy for stroke is promising for preventing excess neuron death and improving functional recovery. Vascular endothelial growth factor (VEGF) is a critical factor for angiogenesis by promoting the proliferation, the survival, and the migration of endothelial cells. Since some ECM components associate with angiogenic proteins and provide an angiogenic microenvironments, such artificial ECMs can effectively enhance angiogenesis and tissue regeneration. In this symposium, I will introduce the supramolecular peptides to manipulate the interaction between nerves and blood vessels. I will also introduce the application of supramolecular peptides for injured brain regeneration.
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