Perlecan controls neurogenesis in the developing telencephalon

Background  

Perlecan is a proteoglycan expressed in the basal lamina of the neuroepithelium during development. Perlecan absence does not impair basal lamina assembly, although in the 55% of the mutants early disruptions of this lamina conducts to exencephaly, impairing brain development. The rest of perlecan-null brains complete its prenatal development, maintain basal lamina continuity interrupted by some isolated ectopias, and are microcephalic. Microcephaly consists of thinner cerebral walls and underdeveloped ganglionic eminences. We have studied the mechanisms that generate brain atrophy in telencephalic areas where basal lamina is intact.     

Adult neurogenesis in the mammalian brain

New neurons are generated throughout life in distinct areas of the mammalian brain. This process, called adult neurogenesis, has challenged previously held concepts about adult brain plasticity and opened novel therapeutic avenues to treat certain neuro-psychiatric diseases. Here, we review the current knowledge regarding the fate and potency of neural stem cells (NSCs), as well as the mechanisms underlying neuronal differentiation and subsequent integration. Furthermore, we discuss the functional significance of adult neurogenesis in health and disease, and offer brief insight into the future directions of the adult neurogenesis field.     

Cellular and molecular mechanisms controlling melatonin release by mammalian pineal glands

1. The pineal gland is regulated primarily by photoperiodic information attaining the organ through a multisynaptic pathway initiated in the retina and the retinohypothalamic tract. 2. Norepinephrine (NE) released from superior cervical ganglion (SCG) neurons that provide sympathetic innervation to the pineal acts through alpha1- and beta 1- adrenoceptors to stimulate melatonin synthesis and release. 3. The increase in cyclic AMP mediated by beta 1-adrenergic activation is potentiated by the increase in Ca2+ flux, inositol phospholipid turnover, and prostaglandin and leukotriene synthesis produced by alpha 1-adrenergic activation. 4. Central pinealopetal connections may also participate in pineal control mechanisms; transmitters and modulators in these pathways include several neuropeptides, amino acids such as gamma-aminobutyric acid (GABA) and glutamate, and biogenic amines such as serotonin, acetylcholine, and dopamine. 5. Secondary regulatory signals for pineal secretory activity are several hormones that act on receptors sites on pineal cells or at any stage of the neuronal pinealopetal pathway.     

哺乳动物神经发育中的Par极性复合体

哺乳动物的神经发育过程极其复杂, 其形态结构和机能变化受到严格的调控。细胞极性是哺乳动物神经发生中最基本的特征之一, 在其调控因素中, Par极性复合体是研究最多的蛋白质。神经发育过程中Par蛋白的分布与量呈现动态变化, 影响细胞连接建立、细胞极性形成、神经突触发生及神经元迁移, 也影响到神经前体细胞的命运。文章主要从胚胎新皮层神经前体细胞及体外培养神经元角度, 总结了近年在Par极性蛋白的细胞内分布、机能及作用机制方面的研究进展。     

Cellular organization of adult neurogenesis in the Common Marmoset

Adult neurogenesis within the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricle (LV) has been most intensely studied within the brains of rodents such as mice and rats. However, little is known about the cell types and processes involved in adult neurogenesis within primates such as the common marmoset (Callithrix jacchus). Moreover, substantial differences seem to exist between the neurogenic niche of the LV between rodents and humans. Here, we set out to use immunohistochemical and autogradiographic analysis to characterize the anatomy of the neurogenic niches and the expression of cell type-specific markers in those niches in the adult common marmoset brain. Moreover, we demonstrate significant differences in the activity of neurogenesis in the adult marmoset brain compared to the adult mouse brain. Finally, we provide evidence for ongoing proliferation of neuroblasts within both the SGZ and SVZ of the adult brain and further show that the age-dependent decline of neurogenesis in the hippocampus is associated with a decrease in neuroblast cells.     

Centrosome regulation and function in mammalian cortical neurogenesis

As the primary microtubule-organizing center in animal cells, centrosomes regulate microtubule cytoskeleton to support various cellular behaviors. They also serve as the base for nucleating primary cilia, the hub of diverse signaling pathways. Cells typically possess one centrosome that contains two inequal centrioles and undergoes semi-conservative duplication during cell division, resulting in two centrosomes with an inherent asymmetry in age and properties. While the centrosome is ubiquitously present, mutations of centrosome proteins are strongly associated with human microcephaly characterized by a small cerebral cortex, underscoring the importance of an intact centrosome in supporting cortical neurogenesis. Here we review recent advances on centrosome regulation and function in mammalian cortical neural progenitors and discuss the implications for a better understanding of cortical neurogenesis and related disease mechanisms.     

Developmental basis for telencephalon expansion in waterfowl: enlargement prior to neurogenesis

Some altricial and some precocial species of birds have evolved enlarged telencephalons compared with other birds. Previous work has shown that finches and parakeets, two species that hatch in an immature (i.e. altricial) state, enlarged their telencephalon by delaying telencephalic neurogenesis. To determine whether species that hatch in a relatively mature (i.e. precocial) state also enlarged their telencephalon by delaying telencephalic neurogenesis, we examined brain development in geese, ducks, turkeys and chickens, which are all precocial. Whereas the telencephalon occupies less than 55 per cent of the brain in chickens and turkeys, it occupies more than 65 per cent in ducks and geese. To determine how these species differences in adult brain region proportions arise during development, we examined brain maturation (i.e. neurogenesis timing) and estimated telencephalon, tectum and medulla volumes from serial Nissl-stained sections in the four species. We found that incubation time predicts the timing of neurogenesis in all major brain regions and that the telencephalon is proportionally larger in ducks and geese before telencephalic neurogenesis begins. These findings demonstrate that the expansion of the telencephalon in ducks and geese is achieved by altering development prior to neurogenesis onset. Thus, precocial and altricial species evolved different developmental strategies to expand their telencephalon.     

哺乳动物成体神经元的再生:内、外环境因子的作用

哺乳动物成体神经元的再生现象是最近三十年才被科学家们所认识并逐渐接受的。随着科研方法与实验技术的发展,在成年哺乳动物的一些特定脑区,比如海马齿状回(Dentate gyrus of the hippocampus)、室下区(Subventricular zone)和杏仁核(Amygdala)中发现了新生细胞。研究表明,内外环境因子可影响成体神经元的再生。具体表现在环境多样性、自主活动、有益社会交往、短日光照、化学刺激以及诸如5—羟色胺和脑源性神经营养因子等神经递质水平的增加,都会促进新生细胞的增生或存活。而负面社会交往及应激激素皮质酮对成体神经元的再生有抑制和降低作用。研究还表明,根据种和性别的差异,类脂醇激素对成体神经元的再生起到促进或抑制作用。最新的实验证实新生细胞在成体中具有显著功能[动物学报49(2)：151—162,2003]。     

Making and repairing the mammalian brain--signaling toward neurogenesis and gliogenesis

Neural stem cells (NSCs) are subscribed extraordinary potential in repair of the damaged nervous system. However, the molecular identity of NSCs has not been established. Most NSC cultures contain large numbers of multipotent, bipotent, and lineage restricted neural progenitors, the majority of which appear to lose neurogenic potential after expansion. This review first discusses the neurogenic to gliogenic switch that is characteristic of progenitor development in vivo and in NSC cultures, and then the cell intrinsic and extrinsic mechanisms regulating the sequential differentiation of neurons and glia. Finally, we discuss potential methods for maintaining the neurogenic potential of NSC cultures after expansion.     

Cellular dynamics and molecular control of the development of organizer-derived cells in quail-chick chimeras

Malformations affecting the nervous system in humans are numerous and various in etiology. Many are due to genetic deficiencies or mechanical accidents occurring at early stages of development. It is thus of interest to reproduce such human malformations in animal models. The avian embryo is particularly suitable for researching the role of morphogenetic movements and genetic signaling during early neurogenesis. The last ten years of research with Nicole Le Douarin in the Nogent Institut have brought answers to questions formulated by Etienne Wolff at the beginning of his career, by showing that Hensen's node, the avian organizer, is at the source of all the midline cells of the embryo and ensures cell survival, growth and differentiation of neural and mesodermal tissues.     

Balancing acts: molecular control of mammalian iron metabolism

Iron is ubiquitous in the environment and in biology. The study of iron biology focuses on physiology and homeostasis-understanding how cells and organisms regulate their iron content, how diverse tissues orchestrate iron allocation, and how dysregulated iron homeostasis leads to common hematological, metabolic, and neurodegenerative diseases. This has provided novel insights into gene regulation and unveiled remarkable links to the immune system.     

Circadian control of neurogenesis

The life-long addition of new neurons has been documented in many regions of the vertebrate and invertebrate brain, including the hippocampus of mammals (Altman and Das, 1965; Eriksson et al., 1998; Jacobs et al., 2000), song control nuclei of birds (Alvarez-Buylla et al., 1990), and olfactory pathway of rodents (Lois and Alvarez-Buylla, 1994), insects (Cayre et al., 1996) and crustaceans (Harzsch and Dawirs, 1996; Sandeman et al., 1998; Harzsch et al., 1999; Schmidt, 2001). The possibility of persistent neurogenesis in the neocortex of primates is also being widely discussed (Gould et al., 1999; Kornack and Rakic, 2001). In these systems, an effort is underway to understand the regulatory mechanisms that control the timing and rate of neurogenesis. Hormonal cycles (Rasika et al., 1994; Harrison et al., 2001), serotonin (Gould, 1999; Brezun and Daszuta, 2000; Beltz et al., 2001), physical activity (Van Praag et al., 1999) and living conditions (Kemperman and Gage, 1999; Sandeman and Sandeman, 2000) influence the rate of neuronal proliferation and survival in a variety of organisms, suggesting that mechanisms controlling life-long neurogenesis are conserved across a range of vertebrate and invertebrate species. The present article extends these findings by demonstrating circadian control of neurogenesis. Data show a diurnal rhythm of neurogenesis among the olfactory projection neurons in the crustacean brain, with peak proliferation during the hours surrounding dusk, the most active period for lobsters. These data raise the possibility that light-controlled rhythms are a primary regulator of neuronal proliferation, and that previously-demonstrated hormonal and activity-driven influences over neurogenesis may be secondary events in a complex circadian control pathway.     

Adult neurogenesis in the mammalian brain: significant answers and significant questions

Adult neurogenesis, a process of generating functional neurons from adult neural precursors, occurs throughout life in restricted brain regions in mammals. The past decade has witnessed tremendous progress in addressing questions related to almost every aspect of adult neurogenesis in the mammalian brain. Here we review major advances in our understanding of adult mammalian neurogenesis in the dentate gyrus of the hippocampus and from the subventricular zone of the lateral ventricle, the rostral migratory stream to the olfactory bulb. We highlight emerging principles that have significant implications for stem cell biology, developmental neurobiology, neural plasticity, and disease mechanisms. We also discuss remaining questions related to adult neural stem cells and their niches, underlying regulatory mechanisms, and potential functions of newborn neurons in the adult brain. Building upon the recent progress and aided by new technologies, the adult neurogenesis field is poised to leap forward in the next decade.