PRD-Class Homeobox Genes in Bovine Early Embryos: Function,Evolution, and Overlapping Roles

Eutherian Totipotent Cell Homeobox (ETCHbox) genes are mammalian-specific PRD-class homeobox genes with conserved expression in the preimplantation embryo but fast-evolving and highly divergent sequences. Here, we exploit an ectopic expression approach to examine the role of bovine ETCHbox genes and show that ARGFX and LEUTX homeodomain proteins upregulate genes normally expressed in the blastocyst; the identities of the regulated genes suggest that, in vivo, the ETCHbox genes play a role in coordinating the physical formation of the blastocyst structure. Both genes also downregulate genes expressed earlier during development and genes associated with an undifferentiated cell state, possibly via the JAK/STAT pathway. We find evidence that bovine ARGFX and LEUTX have overlapping functions, in contrast to their antagonistic roles in humans. Finally, we characterize a mutant bovine ARGFX allele which eliminates the homeodomain and show that homozygous mutants are viable. These data support the hypothesis of functional overlap between ETCHbox genes within a species, roles for ETCHbox genes in blastocyst formation and the change of their functions over evolutionary time.     

同源异形盒基因和肿瘤

最近,美国哈佛药学院的Ｆｏｒｄ发现同源异形盒(ｈｏｍｅｏｂｏｘ)基因在细胞周期、发育以及癌症发展中起着重要的链接作用[1]同源异形盒基因是与细胞正常分化、发育相关的转录因子,最初作为果蝇同源异形突变中的重要座位而得名。此后,陆续有170多个同源异形盒基因在各类物种中被发现。同源异形盒基因的共同点是具有183个核苷酸长度的同源区,编码61个氨基酸。同源异形盒基因同源区表达蛋白通过其ＤＮＡ结合活性及其下游基因转录活性发挥作用。Ｌａｗｒｅｎｃｅ等[2]推测哺乳动物同源异形盒表达蛋白的作用目标为编码细胞外层蛋白质的基因,粘…     

Comparative Biochemistry of the Pineal Gland

The pineal gland is biochemically very active. In mammals, ithas the unique capacity to synthesize the hormone melatonin(N-acetyl-5-methoxy-tryptamine). Although the synthesis of melatoninis confined mainly to the pineal gland of all vertebrates, theeyes and brains of amphibians and fish also can form melatonin.Melatonin is synthesized in the pineal as follows: tryptophan 5-hydroxy-tryptophan serotonin N-acetylserotonin melatonin.The final step is catalyzed by the enzyme, hydroxyindole-O-methyltransferase (HIOMT), which is highly localized in the pinealof all vertebrate species examined. The activity of HIOMT ischanged when animals are kept in constant darkness or light.In rats, highest HIOMT activity is present in constant darkness,while the reverse occurs in avian species. In mammals, informationabout lighting reaches the pineal via the retina inferior accessoryoptic tract preganglionic sympathetic fibers superior cervicalganglia postganglionic fibers pineal parenchymal cells. Lightingmessages reach the hen's pineal via a nonretinal pathway. Studieswith tissue culture indicate that noradrenaline liberated fromsympathetic nerves stimulates synthesis of melatonin. Thereare circadian rhythms in pineal serotonin content which areendogenous and abolished by removal of superior cervical gangliaor by decentralization. There is also a 24-hour rhythm in pinealnoradrenaline. This rhythm is exogenous and is abolished byblinding or cutting the inferior accessory optic tract.     

Homeobox Genes in the Developing Mouse Brain

Abstract: Any list of past and recent findings on vertebrate brain prenatal development would have to include the fundamental roles of homeobox genes, the genes encoding the nuclear regulatory homeodomain proteins. The discovery of homeobox genes and their involvement as master regulatory elements in programing the development of an embryo into a complete adult organism has provided a key to our understanding of ontogenesis. Also, the correlation of mouse developmental mutants and their corresponding human syndromes with mutations in homeobox genes has provided further evidence for the fundamental role of homeobox genes during the vertebrate brain embryonic development. Here, we review the expression patterns and the phenotypes of gene mutations that implicate a large repertoire of mouse homeobox genes in the specification of neuronal functions during brain embryogenesis.     

Mammary Gland Growth Factors: Roles in Normal Development and in Cancer

Normal development of the mammary gland proceeds via interactions between the epithelium and the mesenchyme that start during embryogenesis and continue during pubertal outgrowth and differentiation. The function of specific peptide growth factors that bind members of the receptor tyrosine kinase family and the cytokine receptor family are required at each stage. In many cases the peptides are produced in one compartment and act on receptors in the other compartment. One of the striking differences between normal development and cancer is the loss of this cross-talk. Mammary tumor cells often produce a peptide and express the receptor on the same cell leading to autocrine activation of signaling pathways, a mechanism that is characteristic for cancer cells. We will discuss different peptides in the context of normal development and cancer in this review.Development of the mouse mammary gland begins at embryonic day 10.5 with formation of the milk line, a thickening of the ectoderm that extends from the anterior to the posterior limb buds. By E11.5 five placode pairs invaginate into the surrounding stroma and undergo limited branching morphogenesis. At birth a rudimentary ductal tree is present in a stromal fat pad. At the onset of puberty ovarian hormones induce ductal elongation until the fat pad is filled with a system of ducts and side branches. During pregnancy the glands fill with secretory alveolar units that on parturition produce copius amounts of milk for the offspring. As the pups are weaned, these alveoli are removed by programmed cell death coupled with extensive tissue remodeling, an event termed involution. All these processes are under the control of a wide variety of hormonal and peptide factors. In this review, which is concentrated on peptide growth factors, we will discuss those factors that have important roles in normal development and have been implicated in breast cancer.     

Structure and Function of the Vertebrate Pineal Gland

This review presents data from the literature on structure and function of the pineal gland. Discussed are the histological and ultrastructural characteristics of the gland, its function according to novel results, peculiarity of synthesis and secretion of melatonin and its function, as well as the role of the pineal gland in circadian organization of organisms. The problems of evolution of the pineal function in the row of vertebrates are considered.     

Microdialysis of Melatonin in the Rat Pineal Gland: Methodology and Pharmacological Applications

Abstract: The present study describes the development of a new technique to measure melatonin contents in the pineal gland of freely moving rats, by means of on-line microdialysis. The transcerebral cannula was modified, and a sensitive assay of melatonin, using HPLC with fluori-metric detection, was set up. With this system it is possible to monitor the melatonin levels on-line in the pineal gland during day-and nighttime. The nightly increase in melatonin release was recorded. Tetrodotoxin had an inhibitory effect on nighttime levels, whereas even high concentrations did not alter the daytime level. From this we conclude that neuronal activity is necessary to synthesize melatonin and that during daytime no net neuronal activity is present. Melatonin levels could be greatly enhanced by systemic administration of the β-agonist isoprenaline (ISO). Also, local infusion of ISO or 8-bromoadenosine 3',5'-cyclic monophosphate, an analogue of the second messenger cyclic AMP, resulted in increased melatonin levels, demonstrating the presence of β-adrenergic receptors, coupled to a cyclic AMP-based second messenger system, on the pineal gland. Injection of phenylephrine had no effect on daytime levels. Only when administered during ISO-induced stimulation of melatonin release did it enhance this stimulated release. This proved the regulatory role of α₁-receptors on pinealocytes. The method presented is of special interest for investigating the innervation of the pineal gland and the biochemical processes that regulate the biosynthesis of melatonin. Also, for studies on the diurnal rhythms of melatonin release and factors that influence these rhythms in freely moving animals, this model will be of great value.     

植物同源异型枢基因的研究进展

植物同源异型枢基因是涉及到植物个体发育的一类重要转录因子编码基因.这类基因及其编码蛋白的结构具有明显的保守性,在植物中广泛存在,研究这类基因,对于揭示植物的发育机制具有重要意义.     

Circadian Variation of Cyclic AMP in the Rat Pineal Gland

Abstract: This study was carried out to investigate circadian variation of cyclic AMP contents in the rat pineal glands, using the high-energy microwave radiation technique. The pattern of cyclic AMP concentration in the pineal gland showed a distinct circadian variation, with the maximum level at 0200 and the lowest at 1400. The administration of propranolol completely blocked the dark-induced increase in the pineal cyclic AMP level at 0200, and the administration of isoproterenol induced a threefold, rapid increase in the cyclic AMP level at 1400, although it did not change the level at 0200.     

Expression of C-Type Natriuretic Peptide in the Bovine Pineal Gland

Abstract: The effect of lithium on inositol phospholipid resynthesis in primary cultures of cerebellar granule cells was studied. During activation of phospholipase C by the combined action of a muscarinic agonist and mild depolarization, the levels of inositol phospholipids as well as the inositol phospholipid precursor CMP-phosphatidate appeared highly sensitive to lithium with half-maximal accumulation of CMP-phosphatidate attained at 0.5 m M LiCl, a concentration close to that in the plasma of patients subjected to lithium therapy. Under the same conditions, the effect of lithium on inositol phospholipid metabolism appeared to be mediated by depletion of cytoplasmic free inositol content. This was indicated by the observation that preincubation for 48 h in high extracellular inositol concentrations could decrease or delay the depletion of inositol phospholipids and the accumulation of CMP-phosphatidate induced by 10 m M LiCl. Because even relatively high concentrations of extracellular inositol (500 µ M ) only partially prevented inositol phospholipid depletion, cerebellar granule cells appear to have a comparatively low capacity to accumulate inositol intracellularly, in comparison with other brain cells in culture. The relationship between CMP-phosphatidate accumulation and phospholipase C activity has also been investigated using a range of agonists that have been reported to act on cerebellar granule cells.     

Evolution of The Vertebrate Pineal Gland: The Aanat Hypothesis

The defining feature of the pineal gland is the capacity to function as a melatonin factory that operates on a ∼24 h schedule, reflecting the unique synthetic capacities of the pinealocyte. Melatonin synthesis is typically elevated at night and serves to provide the organism with a signal of nighttime. Melatonin levels can be viewed as hands of the clock. Issues relating to the evolutionary events leading up to the immergence of this system have not received significant attention. When did melatonin synthesis appear in the evolutionary line leading to vertebrates? When did a distinct pineal gland first appear? What were the forces driving this evolutionary trend? As more knowledge has grown about the pinealocyte and the relationship it has to retinal photoreceptors, it has become possible to generate a plausible hypothesis to explain how the pineal gland and the melatonin rhythm evolved. At the heart of the hypothesis is the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (AANAT). The advances supporting the hypothesis will be reviewed here and expanded beyond the original foundation; the hypothesis and its implications will be addressed.     

Evolution of The Vertebrate Pineal Gland: The Aanat Hypothesis

The defining feature of the pineal gland is the capacity to function as a melatonin factory that operates on a ～24 h schedule, reflecting the unique synthetic capacities of the pinealocyte. Melatonin synthesis is typically elevated at night and serves to provide the organism with a signal of nighttime. Melatonin levels can be viewed as hands of the clock. Issues relating to the evolutionary events leading up to the immergence of this system have not received significant attention. When did melatonin synthesis appear in the evolutionary line leading to vertebrates? When did a distinct pineal gland first appear? What were the forces driving this evolutionary trend? As more knowledge has grown about the pinealocyte and the relationship it has to retinal photoreceptors, it has become possible to generate a plausible hypothesis to explain how the pineal gland and the melatonin rhythm evolved. At the heart of the hypothesis is the melatonin rhythm enzyme arylalkylamine N‐acetyltransferase (AANAT). The advances supporting the hypothesis will be reviewed here and expanded beyond the original foundation; the hypothesis and its implications will be addressed.     

植物同源异型基因及同源异型盒基因的研究进展

植物同源异型基因及同源异型盒基因是涉及植物个体发育调节的两类重要转录因子编码基因.近10年来的研究表明,这两类基因及其产物的结构与功能具有明显的差异.深入研究这两类基因的结构与功能对揭示植物的发育机制具有重要意义.     

Some Characteristics of the Night N-Acetyltransferase in the Rat Pineal Gland

Abstract: Following light on at night experiments, N-acetyltransferase level declines, at first rapidly and after 20 min more slowly. We partly characterised the night N-acetyltransferase and the residual N-acetyltransferase 20 min after light on. Both enzymes had pH optimum 6.8 and were inactivated thermally in vitro with a half time of 8 min. Pre-treatment with cycloheximide or puromycin did not block the rise in N-acetyltransferase following isoprotenerol ad-ministration shortly after light on. We propose that night N-acetyltransferase is one enzyme. After light on, the enzyme rapidly deactivates to a less active form. Isoprotenerol applied within a short time may partly reactivate the enzyme.     

PEBP家族基因在植物发育调控中的作用

文章介绍植物PEBP家族的成员组成、系统进化、时空表达特点以及基因功能的研究进展。     

植物同源盒基因的克隆与功能研究

同源盒基因在植物、动物、菌物的广泛存在说明这种结构在真核生物进化的早期就已出现,并暗示其具有重要功能。本文对植物同源盒基因的克隆与功能研究进行了综述,包括同源盒基因编码蛋白的结构特点、类型,并以玉米Knl、水稻OSH1及拟南芥STM为例,介绍了同源盒基因功能研究的现状。现有证据表明,同源盒基因与植物的发育过程有关。