Basic principles and molecular mechanisms of olfactory axon pathfinding

Author(s):  
Yoshihiro Yoshihara ◽  
Kensaku Mori
1997 ◽  
Vol 290 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Yoshihiro Yoshihara ◽  
Kensaku Mori

Author(s):  
Robert Laumbach ◽  
Michael Gochfeld

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.


2005 ◽  
Vol 25 (12) ◽  
pp. 5158-5170 ◽  
Author(s):  
Yieyie Yang ◽  
Erik A. Lundquist

ABSTRACT The roles of actin-binding proteins in development and morphogenesis are not well understood. The actin-binding protein UNC-115 has been implicated in cytoskeletal signaling downstream of Rac in Caenorhabditis elegans axon pathfinding, but the cellular role of UNC-115 in this process remains undefined. Here we report that UNC-115 overactivity in C. elegans neurons promotes the formation of neurites and lamellipodial and filopodial extensions similar to those induced by activated Rac and normally found in C. elegans growth cones. We show that UNC-115 activity in neuronal morphogenesis is enhanced by two molecular mechanisms: when ectopically driven to the plasma membrane by the myristoylation sequence of c-Src, and by mutation of a putative serine phosphorylation site in the actin-binding domain of UNC-115. In support of the hypothesis that UNC-115 modulates actin cytoskeletal organization, we show that UNC-115 activity in serum-starved NIH 3T3 fibroblasts results in the formation of lamellipodia and filopodia. We conclude that UNC-115 is a novel regulator of the formation of lamellipodia and filopodia in neurons, possibly in the growth cone during axon pathfinding.


Development ◽  
1999 ◽  
Vol 126 (19) ◽  
pp. 4201-4212 ◽  
Author(s):  
H. Saueressig ◽  
J. Burrill ◽  
M. Goulding

During early development, multiple classes of interneurons are generated in the spinal cord including association interneurons that synapse with motor neurons and regulate their activity. Very little is known about the molecular mechanisms that generate these interneuron cell types, nor is it known how axons from association interneurons are guided toward somatic motor neurons. By targeting the axonal reporter gene τ-lacZ to the En1 locus, we show the cell-type-specific transcription factor Engrailed-1 (EN1) defines a population of association neurons that project locally to somatic motor neurons. These EN1 interneurons are born early and their axons pioneer an ipsilateral longitudinal projection in the ventral spinal cord. The EN1 interneurons extend axons in a stereotypic manner, first ventrally, then rostrally for one to two segments where their axons terminate close to motor neurons. We show that the growth of EN1 axons along a ventrolateral pathway toward motor neurons is dependent on netrin-1 signaling. In addition, we demonstrate that En1 regulates pathfinding and fasciculation during the second phase of EN1 axon growth in the ventrolateral funiculus (VLF); however, En1 is not required for the early specification of ventral interneuron cell types in the embryonic spinal cord.


Physiology ◽  
2000 ◽  
Vol 15 (3) ◽  
pp. 107-113 ◽  
Author(s):  
Barbara Walzog ◽  
Peter Gaehtgens

About 100 years after the definition of the basic principles of inflammation, the identification of the underlying molecular mechanisms provides a new understanding of the inflammatory response. The specificity and diversity of the adhesion molecules involved in leukocyte extravasation account for the ordered leukocyte recruitment and activation in inflammation.


Nanoscale ◽  
2014 ◽  
Vol 6 (12) ◽  
pp. 6229-6244 ◽  
Author(s):  
Gulaim A. Seisenbaeva ◽  
Vadim G. Kessler

This review summarizes basic principles in the mechanisms of Soft Chemistry synthesis giving access to nanoparticles and nanostructures with controlled architecture, morphology and composition.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Mitsuaki Nishikimi ◽  
Koji Oishi ◽  
Kazunori Nakajima

Numerous studies have investigated the formation of interhemispheric connections which are involved in high-ordered functions of the cerebral cortex in eutherian animals, including humans. The development of callosal axons, which transfer and integrate information between the right/left hemispheres and represent the most prominent commissural system, must be strictly regulated. From the beginning of their growth, until reaching their targets in the contralateral cortex, the callosal axons are guided mainly by two environmental cues: (1) the midline structures and (2) neighboring? axons. Recent studies have shown the importance of axona guidance by such cues and the underlying molecular mechanisms. In this paper, we review these guidance mechanisms during the development of the callosal neurons. Midline populations express and secrete guidance molecules, and “pioneer” axons as well as interactions between the medial and lateral axons are also involved in the axon pathfinding of the callosal neurons. Finally, we describe callosal dysgenesis in humans and mice, that results from a disruption of these navigational mechanisms.


2019 ◽  
Vol 20 (12) ◽  
pp. 3081 ◽  
Author(s):  
Catherine M. Gorick ◽  
John C. Chappell ◽  
Richard J. Price

Many pathological conditions are characterized or caused by the presence of an insufficient or aberrant local vasculature. Thus, therapeutic approaches aimed at modulating the caliber and/or density of the vasculature by controlling angiogenesis and arteriogenesis have been under development for many years. As our understanding of the underlying cellular and molecular mechanisms of these vascular growth processes continues to grow, so too do the available targets for therapeutic intervention. Nonetheless, the tools needed to implement such therapies have often had inherent weaknesses (i.e., invasiveness, expense, poor targeting, and control) that preclude successful outcomes. Approximately 20 years ago, the potential for using ultrasound as a new tool for therapeutically manipulating angiogenesis and arteriogenesis began to emerge. Indeed, the ability of ultrasound, especially when used in combination with contrast agent microbubbles, to mechanically manipulate the microvasculature has opened several doors for exploration. In turn, multiple studies on the influence of ultrasound-mediated bioeffects on vascular growth and the use of ultrasound for the targeted stimulation of blood vessel growth via drug and gene delivery have been performed and published over the years. In this review article, we first discuss the basic principles of therapeutic ultrasound for stimulating angiogenesis and arteriogenesis. We then follow this with a comprehensive cataloging of studies that have used ultrasound for stimulating revascularization to date. Finally, we offer a brief perspective on the future of such approaches, in the context of both further research development and possible clinical translation.


Author(s):  
David P. Bazett-Jones ◽  
Mark L. Brown

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.


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