心脏的左右不对称发育

心脏是脊椎动物发育过程中最早形成的器官之一,心管向右环化打破了左右对称的格局,是左右分化的第一个重要标志.不对称的心管环化和心脏腔室的形态发生是一个相当复杂的过程,人们对其分子机制,特别是心脏定位和不对称发育机理的了解还相当有限.为了探讨心脏的左右不对称发育,重点从形态学和分子水平对近期的研究作了简要的概述.     

左右不对称信号分子Pitx2

同型框基因Pitx2在鸡、小鼠和爪蟾胚胎中不对称地表达在左侧板中胚层和衍生器官(如心脏、肠等)中. 转录因子Pitx2看来是Shh和Nodal等信号分子的下游效应子. Pitx2的错误表达足以产生器官逆位和身体旋转逆向,人类若有Pitx2表达缺陷就可能导致Rieger综合征. Pitx2看来是脊椎动物介导左右不对称的关键且保守的信号分子.     

鸡胚内抗氧化物质的分布与变化

生物体内存在多种内源性抗氧化物质,在生命过程中发挥着基本的防御功能,是人们十分关注的研究领域。本文综述了近年来鸡胚内抗氧化物质的形成与来源等研究成果,分析了鸡胚孵育过程中维生素(A、C、E)、类胡萝卜素、硒、过氧化氢酶和超氧化物歧化酶等主要抗氧化物质的分布与变化,及内源性抗氧化系统的形成,旨在为今后的研究提供有益的科学依据。     

Complete regulation of development throughout metamorphosis of sea urchin embryos devoid of macromeres

The developmental potential of the animal cap (consisting of eight mesomeres) recombined with micromeres or of micromere progeny was examined in sea urchin embryos. The embryos derived from the animal cap recombined with a quartet of micromeres or their descendants developed into four-armed plutei. After feeding, the larvae developed into eight-armed plutei. The left-right polarity of the larvae, recognized by the location of the echinus rudiment, was essentially normal, regardless of the orientation of animal-vegetal polarity in micromeres combining with the animal cap. The larvae had sufficient potential to metamorphose into complete juvenile sea urchins with five-fold radial symmetry. Cell lineage tracing experiments showed that: (i) macromere progeny were not required for formation of the typical pattern of primary mesenchyme cells derived exclusively from large micromeres; (ii) the progeny of large micromeres did not contribute to cells in the endodermal gut with three compartments of normal function; (iii) the presumptive ectoderm had the potential to differentiate into endodermal gut and mesodermal secondary mesenchyme cells, from which pigment cells likely differentiated; and (iv) behavior of the progeny of small micromeres was the same as that in normal embryos through the gastrula stage. These results indicate that the mesomeres respecify their fate under the inductive influence of micromeres so perfectly that complete juvenile sea urchins are produced.     

Left-right development from embryos to brains

Bilateran animals have external bilateral symmetry along the dorsoventral (DV) and anteroposterior (AP) axes. Internal left-right asymmetries appear to be consistently aligned along the left-right (LR) axis with respect to the other axes. Left-right development is most apparent in the directional looping of the cardiac tube, the coiling and placement of the intestines, the positioning of internal organs such as liver, gallbladder, pancreas, and stomach. In addition, there are obvious morphological asymmetries in the brains of some vertebrates and functional left-right asymmetries in the activities of the brain, as assessed by psychological testing, MRI, and the analysis of lesions. There are several fundamental questions: What are the origins of the left-right axis, and are they highly conserved across metazoans? Once the left-right axis is established by the initial breaking of bilateral symmetry, what is the genetic pathway that perpetrates left-right development? What are the cellular and tissue mechanics that lead to morphogenesis during, for example, the looping of the cardiac tube, the coiling of the gut, or asymmetric brain development? Finally, do the asymmetric developmental pathways of each organ system take register from the same initial event that establishes the left-right axis, or are there separate mechanisms that orient heart, gut, and brain left-right asymmetry with respect to the DV and AP axes? These questions are beginning to be experimentally addressed, and papers in this issue of Developmental Genetics make contributions to several aspects in the burgeoning field of left-right development. Recent reviews have summarized the emerging genes and pathways in vertebrate left-right development [Wood, 1997; Harvey, 1998; Ramsdell and Yost, 1998]. Here, I give an overview of the contributions in this issue to the fundamental questions in left-right development. Dev. Genet. 23:159–163, 1998. © 1998 Wiley-Liss, Inc.     

Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis.

KIF3A is a classical member of the kinesin superfamily proteins (KIFs), ubiquitously expressed although predominantly in neural tissues, and which forms a heterotrimeric KIF3 complex with KIF3B or KIF3C and an associated protein, KAP3. To elucidate the function of the kif3A gene in vivo, we made kif3A knockout mice. kif3A-/- embryos displayed severe developmental abnormalities characterized by neural tube degeneration and mesodermal and caudal dysgenesis and died during the midgestational period at approximately 10.5 dpc (days post coitum), possibly resulting from cardiovascular insufficiency. Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels. These results suggest that KIF3A might be involved in mesodermal patterning and in turn neurogenesis.     

鸡胚公母性腺差异表达基因的基因芯片杂交筛选

采用Affymetrix公司鸡基因组芯片对9日龄鸡胚公母性腺总RNA进行了芯片杂交, 并对基因表达谱进行了分析。统计结果显示, 9日龄母鸡性腺表达基因数19 368个, 公鸡性腺表达基因数19 493个; 公母性腺绝对差异表达基因,即公鸡性腺表达而母鸡性腺不表达基因145个, 母鸡性腺表达而公鸡性腺不表达基因189个。绝对差异表达基因功能分类结果显示, 参与细胞组成、细胞加工和分子结合基因占多数, 部分基因参与细胞器组成、代谢加工、生物学调控以及催化反应和细胞信号转导等。值得注意的是, 本研究发现了一些已经报道同性别决定和分化有一定关联的基因, 如ASW、CHD1和SOX9等, 同时也发现了一些未知其同性腺分化和发育有关联的基因和编码假想蛋白的表达序列。进一步分析这些基因和表达序列的生物学功能和表达模式, 将对鸟类性别决定和分化机制的了解提供有益参考。     

A Conserved Role of the Unconventional Myosin 1d in Laterality Determination

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BMP signaling through ACVRI is required for left-right patterning in the early mouse embryo

Vertebrate organisms are characterized by dorsal-ventral and left-right asymmetry. The process that establishes left-right asymmetry during vertebrate development involves bone morphogenetic protein (BMP)-dependent signaling, but the molecular details of this signaling pathway remain poorly defined. This study tests the role of the BMP type I receptor ACVRI in establishing left-right asymmetry in chimeric mouse embryos. Mouse embryonic stem (ES) cells with a homozygous deletion at Acvr1 were used to generate chimeric embryos. Chimeric embryos were rescued from the gastrulation defect of Acvr1 null embryos but exhibited abnormal heart looping and embryonic turning. High mutant contribution chimeras expressed left-side markers such as nodal bilaterally in the lateral plate mesoderm (LPM), indicating that loss of ACVRI signaling leads to left isomerism. Expression of lefty1 was absent in the midline of chimeric embryos, but shh, a midline marker, was expressed normally, suggesting that, despite formation of midline, its barrier function was abolished. High-contribution chimeras also lacked asymmetric expression of nodal in the node. These data suggest that ACVRI signaling negatively regulates left-side determinants such as nodal and positively regulates lefty1. These functions maintain the midline, restrict expression of left-side markers, and are required for left-right pattern formation during embryogenesis in the mouse.     

全胚连续消化制备鸡胚成纤维细胞技术研究

在一定条件下,将全胚置胰酶消化液中搅拌连续消化,建立了全胚连续消化制备鸡胚成纤维细胞（ＣｈｉｃｋｅｎＥｍｂｒｙｏＦｉｂｒｏｂｌａｓｔ,ＣＥＦ）技术,用该技术制备ＣＥＦ,每胚细胞产量达２．０亿个以上,是传统技术的２～３倍．所制备的细胞活性高,贴壁性强,分散度好,培养的单层均匀．以这种细胞单层为基质增殖病毒,病毒产量不低于传统方法制备的细胞单层的水平．     

Cease and desist: modulating short-range Dpp signalling in the stem-cell niche

Drosophila ovarian germline stem cells (GSCs) are maintained by the extracellular BMP2/4 orthologue Dpp, which is produced from the surrounding somatic niche. The Dpp signal has a short range; it induces a response in GSCs within the niche, but is rapidly extinguished in their progeny only one cell-diameter away. To ensure the correct balance between stem-cell maintenance and differentiation, several regulatory mechanisms that modulate the Dpp signal at many stages of the pathway have been described. Here, we discuss the nature of the ovarian Dpp signal and review the catalogue of mechanisms that regulate it, demonstrating how the exquisite modulation of Dpp signalling in this context can result in precise and robust control of stem-cell fate. This modulation is applicable to other stem-cell environments that use BMPs as a niche signal, and the regulatory mechanisms are conceptually relevant to several other stem-cell systems.     

几种生理因素对子房未授粉南瓜胚形成的影响

以南瓜品种‘蜜本’为试材,研究生理因素影响未授粉南瓜胚形成的结果表明：开花前1d的子房最适宜于胚的诱导;胚诱导前以35℃高温处理6d后胚形成能力显著提高;高浓度2,4-D促进胚的发生,抑制愈伤组织的形成;加有4．0mg··L^-1 2,4-D、0．5mg·L^-1 NAA和0．5mg·L^-1 6-BA的MS培养基上的出胚率最高（20．6±3．8）％,每个子房块的平均出胚数达11．3±3．2。