Signaling through focal adhesion kinase

Integrin receptor binding to extracellular matrix proteins generates intracellular signals via enhanced tyrosine phosphorylation events that are important for cell growth, survival, and migration. This review will focus on the functions of the focal adhesion kinase (FAK) protein-tyrosine kinase (PTK) and its role in linking integrin receptors to intracellular signaling pathways. FAK associates with several different signaling proteins such as Src-family PTKs, p130^Cas, Shc, Grb2, PI 3-kinase, and paxillin. This enables FAK to function within a network of integrin-stimulated signaling pathways leading to the activation of targets such as the ERK and JNK/mitogen-activated protein kinase pathways. Focus will be placed on the structural domains and sites of FAK tyrosine phosphorylation important for FAK-mediated signaling events and how these sites are conserved in the FAK-related PTK, Pyk2. We will review what is known about FAK activation by integrin receptor-mediated events and also non-integrin stimuli. In addition, we discuss the emergence of a consensus FAK substrate phosphorylation sequence. Emphasis will also be placed on the role of FAK in generating cell survival signals and the cleavage of FAK during caspase-mediated apoptosis. An in-depth discussion will be presented of integrin-stimulated signaling events occurring in the FAK knockout fibroblasts (FAK⁻) and how these cells exhibit deficits in cell migration. FAK re-expression in the FAK⁻ cells confirms the role of this PTK in the regulation of cell morphology and in promoting cell migration events. In addition, these results reinforce the potential role for FAK in promoting an invasive phenotype in human tumors.  

VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia

Vascular endothelial growth factor (VEGF-A) is a major regulator of blood vessel formation and function. It controls several processes in endothelial cells, such as proliferation, survival, and migration, but it is not known how these are coordinately regulated to result in more complex morphogenetic events, such as tubular sprouting, fusion, and network formation. We show here that VEGF-A controls angiogenic sprouting in the early postnatal retina by guiding filopodial extension from specialized endothelial cells situated at the tips of the vascular sprouts. The tip cells respond to VEGF-A only by guided migration; the proliferative response to VEGF-A occurs in the sprout stalks. These two cellular responses are both mediated by agonistic activity of VEGF-A on VEGF receptor 2. Whereas tip cell migration depends on a gradient of VEGF-A, proliferation is regulated by its concentration. Thus, vessel patterning during retinal angiogenesis depends on the balance between two different qualities of the extracellular VEGF-A distribution, which regulate distinct cellular responses in defined populations of endothelial cells.  

Cell migration: Rho GTPases lead the way

Rho GTPases control signal transduction pathways that link cell surface receptors to a variety of intracellular responses. They are best known as regulators of the actin cytoskeleton, but in addition they control cell polarity, gene expression, microtubule dynamics and vesicular trafficking. Through these diverse functions, Rho GTPases influence many aspects of cell behavior. This review will focus specifically on their role in cell migration.  

Fibronectin in early avian embryos: Synthesis and distribution along the migration pathways of neural crest cells

Summary Immunoperoxidase labelling for fibronectin (FN) in chick embryos showed FN-positive basement membranes surrounding the neural crest cell population prior to crest-cell migration. At cranial levels, crest cells migrated laterally into a large cell-free space. Initially they moved as a tongue of cells contacting the FN-positive basement membrane of the ectoderm, but later the crest cell population expanded into space further from the ectoderm, until eventually the entire cranial cell-free space was occupied by mesenchyme cells. This was accompanied by the appearance of FN among the crest cells. At trunk levels, crest cells entered a relatively small space already containing FN-positive extracellular material. At later stages the migration of trunk crest cells broadly matched the distribution of FN. In vitro, chick and quail embryo ectoderm, endoderm, somites, notochord and neural tube synthesized and organized fibrous FN-matrices, as shown by immunofluorescence. Ectoderm and endoderm deposited this matrix only on the substrate face. The FN content of endoderm and neural tube matrices was transient, the immunofluorescence intensity declining after 1–2 days in culture. Some crest cells of cranial and sacral axial levels synthesized FN. Our data suggests that these were the earliest crest cells to migrate from these levels. This ability may be the first expression of mesenchymal differentiation in these crest cells, and in vivo enable them to occupy a large space. Almost all crest cells from cervico-lumbar axial levels were unable to synthesize FN. In vivo, this inability may magnify the response of these crest cells to FN provided by the neighbouring embryonic tissues.  

人骨髓间充质干细胞在成年大鼠脑内的迁移及分化

骨髓间充质干细胞 (mesenchymalstemcells,MSCs)是目前备受关注的一类具有多向分化潜能的组织干细胞 ,体外可以分化为骨、软骨、脂肪等多种细胞。因此 ,MSCs是细胞治疗和基因治疗的种子细胞之一。为了探索MSCs的迁移和分化趋势 ,为帕金森病 (Parkinsondisease,PD)的干细胞治疗提供理论和实验依据 ,本实验将体外扩增并转染增强型绿色荧光蛋白 (enhancedgreenfluorescentprotein ,EGFP)的人骨髓MSCs注入PD大鼠脑内纹状体 ,观察了人骨髓MSCs在大鼠脑内的存活、迁移、分化以及注射MSCs前后大鼠的行为变化。结果表明 ,人骨髓MSCs在大鼠脑内可存活较长时间 ( 10周以上 ) ;随着时间的延长 ,MSCs迁移范围扩大 ,分布于纹状体、胼胝体、皮质以及脑内血管壁 ;免疫组化法检测证实MSCs在大鼠脑内表达人神经丝蛋白 (neurofilament,NF)、神经元特异性烯醇化酶 (neuron specificeno lase,NSE)以及胶质原纤维酸性蛋白 ( glialfibrillaryacidprotein ,GFAP) ;PD大鼠的异常行为有所缓解 ,转圈数由 8 86±2 0 9r/min下降到 4 87± 2 0 6r/min ,统计学分析P <0 0 5为差异显著。以上观察结果表明 ,骨髓MSCs有望成为治疗PD的种子细胞  

Tracing origins and migration of wildlife using stable isotopes: a review

To understand the ecology of migratory animals it is important to link geographic regions used by individuals including breeding, wintering, and intermediate stopover sites. Previous conventional approaches used to track animal movements have relied on extrinsic markers and typically the subsequent recovery of individuals. This approach has generally been inappropriate for most small, or non-game animals. The use of intrinsic markers such as fatty acid profiles, molecular DNA analyses, and the measurement of naturally occurring stable isotopes in animal tissues offer alternative approaches. This paper reviews the use of stable isotope analyses (primarily δ¹³C, δ¹⁵N, δ³⁴S, δD, δ⁸⁷Sr) to trace nutritional origin and migration in animals. This approach relies on the fact that foodweb isotopic signatures are reflected in the tissues of organisms and that such signatures can vary spatially based on a variety of biogeochemical processes. Organisms moving between isotopically distinct foodwebs can carry with them information on the location of previous feeding. Such an approach has been used to track animal use of inshore versus offshore, marine versus freshwater, terrestrial C₃ versus marine, terrestrial mesic versus xeric, and C₃ versus C₄ or Crassulacean acid metabolism foodwebs. More recently, the use of stable hydrogen isotope analyses (δD) to link organisms to broad geographic origin in North America is based on large-scale isotopic contours of growing-season average δD values in precipitation. This technique, especially when combined with the assay of other stable isotopes, will be extremely useful in helping to track migration and movement of a wide range of animals from insects to birds and mammals. Future research to refine our understanding of natural and anthropogenic-induced isotopic gradients in nature, and to explore the use of stable isotopes of other elements, is recommended. Received: 1 July 1998 / Accepted: 9 December 1998  

洞庭湖区东方田鼠迁移的研究

洞庭湖区东方田鼠以湖滩上的芦苇＋荻或薹草沼泽为最适栖息地，枯水季节，多在其上生长、繁殖。汛期，随着湖水上涨，湖滩面积缩小，东方田鼠在拥挤的的压力下或直接被洪水所迫，越过防洪堤迁入垸内。东方田鼠在湖滩及农田间的迁移主要取决于湖水水位及种群密度，无固定的迁移时间。迁入垸内的东方田鼠主要分布于靠近防洪堤一带，其捕获率随着与防洪堤距离的增加而递减。个体较大的东方田鼠迁移距离较远。在迁移期，迁入垸内的东方田鼠的性比在不同的距离上无显著差异。湖水回落时，东方田鼠随湖滩出露而迁回沼泽草地。回迁时，个体较大的雄性首先回迁的比例较高。迁入垸内的东方田鼠，栖息在荒坡地的种群密度大于在农田中的种群密度；东方田鼠不在农田越冬，小部分可在岗地荒坡中越冬，但少有增殖。按迁移动因看，此种迁移乃洪水逼迫所至，而由逼迫外迁和自动回迁构成循环，保证了种群对湖区特殊环境的适应。  

行为的结构、刚性和多样性

有关动物行为的定义、结构和多样性是一个被长期忽视的研究领域。然而，动物行为多样性不仅是一个生物多样性基础理论问题，也与濒危动物的成功保护有关。本文定义了动物行为以及行为的刚性与弹性，探讨了行为表达的空间条件以及生境因素与行为多样性之间的关系。我们发现雌雄大熊猫个体在较大的活动空间里的发情行为表现的频次及活动频率显著地高于那些在较小的空间里的雌雄个体，说明活动空间对雄性或雌性大熊猫的发情行为有显著影响。圈养空间影响麋鹿的社会行为、通讯行为和聚群行为。圈养在小圈中的麋鹿没有出现同性聚群现象，当圈养麋鹿野放后即表现出这种现象。圈养环境中长大的动物个体由于缺乏行为的表达空间，仅仅表现出刚性大的行为，丧失了许多弹性大的行为，从而导致动物行为的多样性下降。对那些生活在开阔草原和荒漠上的野生有蹄类动物实施迁地保护时，必须考虑其逃逸空间，为那些动物建立自然保护区时，则必须考虑其迁移空间。此外，动物行为的多样性与生境元素有关。我们应当给圈养动物提供复杂而多样的环境，以增加圈养野生动物表达寻找食物、建立领域、筑巢和避开不利环境等行为的可能性，维持濒危个体的行为多样性。  

A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8, is useful for cell therapy to repair damaged liver

We previously reported a new in vivo model named as "GFP/CCl(4) model" for monitoring the transdifferentiation of green fluorescent protein (GFP) positive bone marrow cell (BMC) into albumin-positive hepatocyte under the specific "niche" made by CCl(4) induced persistent liver damage, but the subpopulation which BMCs transdifferentiate into hepatocytes remains unknown. Here we developed a new monoclonal antibody, anti-Liv8, using mouse E 11.5 fetal liver as an antigen. Anti-Liv8 recognized both hematopoietic progenitor cells in fetal liver at E 11.5 and CD45-positive hematopoietic cells in adult bone marrow. We separated Liv8-positive and Liv8-negative cells and then transplanted these cells into a continuous liver damaged model. At 4 weeks after BMC transplantation, more efficient repopulation and transdifferentiation of BMC into hepatocytes were seen with Liv8-negative cells. These findings suggest that the subpopulation of Liv8-negative cells includes useful cells to perform cell therapy on repair damaged liver.