Novel brain wiring functions for classical morphogens: a role as graded positional cues in axon guidance

During embryonic development, morphogens act as graded positional cues to dictate cell fate specification and tissue patterning. Recent findings indicate that morphogen gradients also serve to guide axonal pathfinding during development of the nervous system. These findings challenge our previous notions about morphogens and axon guidance molecules, and suggest that these proteins, rather than having sharply divergent functions, act more globally to provide graded positional information that can be interpreted by responding cells either to specify cell fate or to direct axonal pathfinding. This review presents the roles identified for members of three prominent morphogen families--the Hedgehog, Wnt and TGFbeta/BMP families--in axon guidance, and discusses potential implications for the molecular mechanisms underlying their guidance functions.     

Cortical mechanisms and cues for action

Monkeys have more highly developed brains and are more intelligent than rats; yet rats learn some tasks as efficiently as monkeys. For example, rats are as quick at discovering which of two doors hides food or how to open the doors. Presumably tasks of this sort do not greatly tax cortical associative mechanisms since the animals have only to cumulate facts about objects. It is argued that cortical mechanisms are crucial for the ability to relate together information that is presented at different times or in different places. After removal of parts of frontal cortex monkeys can still associate cues that are presented together but they are poor at relating cues that are presented apart.     

Secreted inducers in vertebrate eye development: more functions for old morphogens

Cell signaling molecules secreted from strategically localized positions coordinate cell behavior to enable progressive specification of embryonic tissues. These molecules converge on a few signaling pathways that are reiteratively used in different tissues at different times for generating cell type-specific patterns of gene expression. Although our current knowledge of the system is fragmentary, eye development seems to follow this general strategy. In line with this idea, recent studies have added new information on how Fgf and Wnt signaling participates in the formation of the eye field. In addition, later on in development, Fgf controls the onset of retinal neurogenesis and Shh and GDF11 control its feedback regulation.     

Cortical development: the sources of spontaneous patterned activity

A recent study has found that spontaneous neural activity in the developing visual cortex has two distinct origins - local intracortical circuits and spontaneous activity in the retina.     

Cortical development: the art of generating cell diversity

The fascinating question of how the enormous diversity of neuronal and glial cells in the cerebral cortex is generated during development was recently discussed at a meeting on cortical development and stem cells in Greece. What emerged from this meeting is an equally fascinating answer, namely that precursor diversity at rather early stages of development anticipates later cell type diversity.     

Netrins: versatile extracellular cues with diverse functions

Netrins are secreted proteins that were first identified as guidance cues, directing cell and axon migration during neural development. Subsequent findings have demonstrated that netrins can influence the formation of multiple tissues, including the vasculature, lung, pancreas, muscle and mammary gland, by mediating cell migration, cell-cell interactions and cell-extracellular matrix adhesion. Recent evidence also implicates the ongoing expression of netrins and netrin receptors in the maintenance of cell-cell organisation in mature tissues. Here, we review the mechanisms involved in netrin signalling in vertebrate and invertebrate systems and discuss the functions of netrin signalling during the development of neural and non-neural tissues.     

Plant sphingolipids: structural diversity,biosynthesis, first genes and functions

In mammals and Saccharomyces cerevisiae, sphingolipids have been a subject of intensive research triggered by the interest in their structural diversity and in mammalian pathophysiology as well as in the availability of yeast mutants and suppressor strains. More recently, sphingolipids have attracted additional interest, because they are emerging as an important class of messenger molecules linked to many different cellular functions. In plants, sphingolipids show structural features differing from those found in animals and fungi, and much less is known about their biosynthesis and function. This review focuses on the sphingolipid modifications found in plants and on recent advances in the functional characterization of genes gaining new insight into plant sphingolipid biosynthesis. Recent studies indicate that plant sphingolipids may be also involved in signal transduction, membrane stability, host-pathogen interactions and stress responses.     

Heat shock proteins 90 kDa: diversity, structure, functions

The review presents data on diversity, structure, functions and gene expression of the high conserved family of heat shock proteins 90 kDa (Hsp90). They are specialized molecular chaperones that fulfill the folding, maintenance of structural integrity and conformational regulation of a subset of proteins involved in important cellular processes, such as transduction of signals, cell cycle control etc. A composition and functioning of the Hsp90 chaperone machine are considered. Hsp90s play a significant role in growth and development of organisms carrying out conformational regulation of many regulatory proteins and protecting cells under stress. The review summarizes the results of investigations of different organisms, mainly animals and yeasts, with emphasis on the facts on Hsp90s in plants.     

l-Amino acid oxidases from microbial sources: types,properties, functions,and applications

l-Amino acid oxidases (LAAOs), which catalyze the stereospecific oxidative deamination of l-amino acids to α-keto acids and ammonia, are flavin adenine dinucleotide-containing homodimeric proteins. l-Amino acid oxidases are widely distributed in diverse organisms and have a range of properties. Because expressing LAAOs as recombinant proteins in heterologous hosts is difficult, their biotechnological applications have not been thoroughly advanced. LAAOs are thought to contribute to amino acid catabolism, enhance iron acquisition, display antimicrobial activity, and catalyze keto acid production, among other roles. Here, we review the types, properties, structures, biological functions, heterologous expression, and applications of LAAOs obtained from microbial sources. We expect this review to increase interest in LAAO studies.     

Multiple functions of a Drosophila homeotic gene, zeste-white 3, during segmentation and neurogenesis

Lack of both maternal and zygotic gene activity at the zeste-white 3 (zw3) locus causes severe developmental transformations. Embryos derived from germ cells that lack zw3+ gene activity die during embryogenesis and have a phenotype that is similar to that of embryos mutant for the segment polarity gene naked (nkd). In both nkd and germ line clone-derived zw3 embryos the pattern elements derived from the anterior-most part of each segment, the denticle belts, are deleted. Similar abnormal patterns of the zygotically expressed genes engrailed and Ultrabithorax are detected in both mutants, suggesting that the two genes are involved in the same developmental process. Additionally, the induction of clones of zw3 mutant cells in imaginal discs causes homeotic transformations of noninnervated hair cells into innervated sensory bristles. The multiple roles of zw3 during development and its possible interactions with the zygotic gene nkd are discussed.     

Novel functions of GABA signaling in adult neurogenesis

Neurotransmitter gamma-aminobutiric acid （GABA） through ionotropic GABAA and metabotropic GABAB receptors plays key roles in modulating the development, plasticity and function of neuronal networks. GABA is inhibitory in mature neurons but excitatory in immature neurons, neuroblasts and neural stem/progenitor cells （NSCs/ NPCs）. The switch from excitatory to inhibitory occurs following the development of glutamatergic synaptic input and results from the dynamic changes in the expression of Na＋/K＋/2CF co-transporter NKCC1 driving CF influx and neuron-specific K＋/Cl co-transporter KCC2 driving Cl efflux. The developmental transition of KCC2 expression is regulated by Disrupted-in-Schizophrenia 1 （DISC1） and brain-derived neurotrophic factor （BDNF） signaling. The excitatory GABA signaling during early neurogenesis is important to the activity/experience-induced regulation of NSC quiescence, NPC proliferation, neuroblast migration and new-born neuronal maturation/functional integration. The inhibitory GABA signaling allows for the sparse and static functional networking essential for learning/memory development and maintenance.     

Xyloglucan endotransglycosylases: diversity of genes, enzymes and potential wall-modifying functions.

Plant cells are enclosed by walls that define the shapes and sizes of cells and mediate cell-to-cell contact. The dynamics of plant growth, morphogenesis and differentiation require concomitant modifications of the walls. A class of enzymes known as xyloglucan endotransglycosylases have the potential to enzymatically modify wall components, but although their biochemical activity has been defined, the physiological roles of xyloglucan endotransglycosylases remain undefined. Xyloglucan endotransglycosylases are encoded by large gene families, and in an attempt to clarify their physiological role, the diverse regulation of the genes and properties of the proteins are being determined.     

Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice

Background

Alzheimer''s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions, extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles within neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role in learning and memory processes and its abnormal regulation might account for cognitive impairments associated with AD.

Methodology/Principal Findings

The double transgenic (Tg) CRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein), aged 2 and 6 months, were used to examine in vivo the effects of 5 weeks lithium treatment. BrdU labelling showed a decreased neurogenesis in the subgranular zone of Tg mice compared to non-Tg mice. The decrease of hippocampal neurogenesis was accompanied by behavioural deficits and worsened with age and pathology severity. The differentiation into neurons and maturation of the proliferating cells were also markedly impaired in the Tg mice. Lithium treatment to 2-month-old Tg mice significantly stimulated the proliferation and neuron fate specification of newborn cells and fully counteracted the transgene-induced impairments of cognitive functions. The drug, by the inhibition of GSK-3β and subsequent activation of Wnt/ß-catenin signalling promoted hippocampal neurogenesis. Finally, the data show that the lithium''s ability to stimulate neurogenesis and cognitive functions was lost in the aged Tg mice, thus indicating that the lithium-induced facilitation of neurogenesis and cognitive functions declines as brain Aβ deposition and pathology increases.

Conclusions

Lithium, when given on time, stimulates neurogenesis and counteracts AD-like pathology.