scholarly journals From embryonic fascicles to adult tracts: organization of neuropile from a developmental perspective

1984 ◽  
Vol 112 (1) ◽  
pp. 45-64
Author(s):  
M. Bastiani ◽  
K. G. Pearson ◽  
C. S. Goodman

We discuss ideas emerging from our studies on selective axonal fasciculation in the grasshopper embryo that have implications for the organization of the adult neuropile in insects and perhaps other animals. While one of our laboratories has been studying the embryonic development of the G neurone (in the mesothoracic segment) and its lineal homologues (in other segments), the other has been studying the morphology and physiology of this same neurone and its segmental homologues in the adult nervous system. Our embryonic studies show that the growth cone of the G neurone selectively fasciculates with the A/P fascicle in preference to all other longitudinal axon fascicles at it turns anteriorly. The homologues of G in other thoracic and abdominal segments fasciculate in this same bundle. However, early in their morphological differentiation, they reveal interesting segmental differences. Our studies on the adult nervous system show that the segmental homologues of the G neurone share many properties in common (e.g. axons in the LDT: lateral dorsal tract) while other features are quite different. The notion emerging from these studies is that a basic segmentally-repeated pattern arises during embryogenesis: a stereotyped axonal scaffold upon which growth cones faithfully fasciculate. Evolutionary plasticity allows the specialization of lineally equivalent neurones in different segments within the context of the neuropilar neighbourhood that they find themselves in as a consequence of their selective fasciculation.

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3703-3712 ◽  
Author(s):  
A. Hidalgo ◽  
J. Urban ◽  
A.H. Brand

Glial cells are thought to play a role in growth cone guidance, both in insects and in vertebrates. In the developing central nervous system of the Drosophila embryo, the interface glia form a scaffold prior to the extension of the first pioneer growth cones. Growing axons appear to contact the glial scaffold as the axon tracts are established. We have used a novel technique for targeted cell ablation to kill the interface glia and thus to test their role in establishment of the embryonic axon tracts. We show that ablation of the interface glia early in development leads to a complete loss of the longitudinal axon tracts. Ablation of the glia later in embryonic development results in defects comprising weakening and loss of axon fascicles within the connectives. We conclude that the interface glia are required first for growth cone guidance in the formation of the longitudinal axon tracts in the Drosophila embryo and then either to direct the follower growth cones, or to maintain the longitudinal axon tracts.


The intention of the author in the present paper, is, not to bring forwards any new facts, but to take a general review of the inferences deducible from the series of facts detailed by him in previous papers communicated to this Society. He divides the nerves into two classes, essentially differing in their functions. The first comprehends those nerves, which, proceeding directly from the brain and spinal cord to other parts, convey in the one case to those parts the influence of those organs only from which they originate, and thus excite to con­traction the muscles of voluntary motion ; and in the other case transmit to the sensorium impressions made on the parts to which they are distributed. The second class comprises what may betermed the Ganglionic nerves, or those which enter ganglions, pro­perly so called; that term being limited to such protuberances only as receive branches of nerves proceeding from the brain and spiral cord. These nerves are distributed more especially to the vital or­ gans, as the thoracic and abdominal viscera, and to the muscles sub­servient to their functions. The nerves belonging to this class also convey impressions to the sensorium, and occasionally excite the muscles of involuntary motion, which, in common with all muscles, possess an inherent power of contractility dependent solely on their own mechanism, and which in ordinary cases are excited by stimuli peculiar to themselves. But the most important function of the gan­glionic nerves, is that of supporting the processes of secretion and assimilation, which require for their performance the combined influ­ence of the whole brain and spinal cord. Viewed as a whole, the system of ganglionic nerves, therefore, constitutes, in the strictest sense, a vital organ. Thus the sensorium, though connected by means of the cerebral and spinal nerves only partially with the organs of sense and voluntary motion, is, by means of the ganglionic nerves, connected generally with all the functions of the animal body. Hence affections of the stomach and other vital organs extend their influence over every part of the frame; while those of a muscle of voluntary motion, or even of an organ of sense, although possessing greater sensibility, are confined to the injured part. From a due consideration of the phenomena of the nervous system, it would appear that they imply the operation of more than one prin­ciple of action. The sensorial power is wholly distinct from the ner­vous power; the former residing chiefly in the brain, while the latter belongs equally to the spinal cord and brain, and may be exercised independently of the sensorial power. In like manner, the muscular power resides in the muscles, and may be called into action by various irritations independently of the nervous power, though fre­quently excited by the action of that power. The muscles of volun­tary motion are subjected to the sensorial power through the inter­vention of the nervous system; and those of involuntary motion are also, under certain circumstances, capable of being excited through the nerves by the sensorial power, particularly when under the influ­ence of the passions. The same observation applies also to other actions which properly belong to the nervous power, such as the evolution of caloric from the blood, and the various processes of se­cretion and of assimilation. That the nervous power is in these instances merely the agent of other powers, and is independent of the peculiar organization of the nerves, is proved by the same effects being produced by galvanism, transmitted through conductors diffe­rent from the nerves. The successive subordination of these several powers is shown during death, when the sensorial functions are the first to cease, and the animal no longer feels or wills, but yet the nervous power still continues to exist, as is proved by the nerves be­ing capable, when stimulated, of exciting contractions in the muscles, both of voluntary and of involuntary motion,of producing the evolution of caloric and of renewing the processes of secretion. In like manner the power of contraction, inherent in the muscular fibre, survives the destniction of both the sensorial and nervous powers, having an existence independent of either, although in the entire state of the functions they are subjected to the entire influence of both.


1993 ◽  
Vol 105 (1) ◽  
pp. 203-212 ◽  
Author(s):  
P. Clark ◽  
S. Britland ◽  
P. Connolly

Neurite growth cones detect and respond to guidance cues in their local environment that determine stereotyped pathways during development and regeneration. Micropatterns of laminin (which was found to adsorb preferentially to photolithographically defined hydrophobic areas of micropatterns) were here used to model adhesive pathways that might influence neurite extension. The responses of growth cones were determined by the degree of guidance of neurite extension and also by examining growth cone morphology. These parameters were found to be strongly dependent on the geometry of the patterned laminin, and on neuron type. Decreasing the spacing of multiple parallel tracks of laminin alternating with non-adhesive tracks, resulted in decreased guidance of chick embryo brain neurons. Single isolated 2 microns tracks strongly guided neurite extension whereas 2 microns tracks forming a 4 microns period multiple parallel pattern did not. Growth cones appear to be capable of bridging the narrow non-adhesive tracks, rendering them insensitive to the smaller period multiple parallel adhesive patterns. These observations suggest that growth cones would be unresponsive to the multiple adhesive cues such as would be presented by oriented extracellular matrix or certain axon fascicle structures, but could be guided by isolated adhesive tracks. Growth cone morphology became progressively simpler on progressively narrower single tracks. On narrow period multiple parallel tracks (which did not guide neurite extension) growth cones spanned a number of adhesive/non-adhesive tracks, and their morphology suggests that lamellipodial advance may be independent of the substratum by using filopodia as a scaffold. In addition to acting as guidance cues, laminin micropatterns also appeared to influence the production of primary neurites and their subsequent branching. On planar substrata, dorsal root ganglion neurons were multipolar, with highly branched neurite outgrowth whereas, on 25 microns tracks, neurite branching was reduced or absent, and neuron morphology was typically bipolar. These observations indicate the precision with which growth cone advance may be controlled by substrata and suggest a role for patterned adhesiveness in neuronal morphological differentiation, but also highlight some of the limitations of growth cone sensitivity to substratum cues.


2019 ◽  
Author(s):  
Leah Kershner ◽  
Taylor Bumbledare ◽  
Paige Cassidy ◽  
Samantha Bailey ◽  
Kristy Welshhans

AbstractLocal translation regulates the formation of appropriate connectivity in the developing nervous system. However, the localization and molecular mechanisms underlying this translation within growth cones is not well understood. Receptor for activated C kinase 1 (RACK1) is a multi-functional ribosomal scaffolding protein that interacts with β-actin mRNA. We recently showed that RACK1 localizes to and regulates the formation of point contacts, which are adhesion sites that control growth cone motility. This suggests that local translation occurs at these adhesion sites that are important for axonal pathfinding, but this has not been investigated. Here, we show that RACK1 is required for BDNF-induced local translation of β-actin mRNA in growth cones. Furthermore, the ribosomal binding function of RACK1 regulates point contact formation, and axon growth and guidance. We also find that local translation of β-actin occurs at point contacts. Taken together, we show that adhesions are a targeted site of local translation within growth cones, and RACK1 is critical to the formation of point contacts and appropriate neural development. These data provide further insight into how and where local translation is regulated, and thereby leads to appropriate connectivity formation in the developing nervous system.


Author(s):  
C.V. Williams ◽  
S.B. Kater

Since calcium is a key second messenger in both the developmental formation and adult function of the nervous system, the ability to rapidly image changes in this molecule has added greatly to our understanding of how development of the nervous system is regulated. The nervous system is comprised of billions of neurons and glial cells that establish characteristic patterns of connections during development. Neurons extend processes that often must grow long distances to establish appropriate synaptic connections. Neurons perform a pathfinding behavior largely via the highly dynamic behavior of the neuronal growth cone at the distal tip of elongating processes. The motile behavior characteristic of growth cones allows the growth cone to survey the local environment, read local cues and respond to those cues with a change in behavior. A variety of cues are now known to direct growth cones (e.g. electrical activity, depolarization, growth factors, mechanical factors, neurotransmitters, substrate factors). This collection of factors includes both growth promoting and growth inhibitory influences.


2003 ◽  
Vol 51 (4) ◽  
pp. 445-454 ◽  
Author(s):  
Arthur T. Legg ◽  
Timothy P. O'Connor

The generation of a functional nervous system is dependent on precise path-finding of axons during development. This pathfinding is directed by the distribution of local and long-range guidance cues, the latter of which are believed to be distributed in gradients. Gradients of guidance cues have been associated with growth cone function for over a hundred years. However, little is known about the mechanisms used by growth cones to respond to these gradients, in part owing to the lack of identifiable gradients in vivo. In the developing grasshopper limb, two gradients of the semaphorin Sema-2a are necessary for correct neuronal pathfinding in vivo. The gradients are found in regions where growth cones make critical steering decisions. Observations of different growth cone behaviors associated with these gradients have provided some insights into how growth cones respond to them. Growth cones appear to respond more faithfully to changes in concentration, rather than absolute levels, of Sema-2a expression, whereas the absolute levels may regulate growth cone size.


Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 4121-4131 ◽  
Author(s):  
K.P. Menon ◽  
K. Zinn

Tyrosine kinase signaling pathways are essential for process outgrowth and guidance during nervous system development. We have examined the roles of tyrosine kinase activity in programming growth cone guidance decisions in an intact nervous system in which neurons can be individually identified. We applied the tyrosine kinase inhibitors herbimycin A and genistein to whole 40% grasshopper embryos placed in medium, or injected the inhibitors into intact grasshopper eggs. Both inhibitors caused interneuronal axons that normally would grow along the longitudinal connectives to instead leave the central nervous system (CNS) within the segmental nerve root and grow out toward the body wall muscles. In addition, herbimycin A produced pathfinding errors in which many longitudinal axons crossed the CNS midline. To study how this drug affected guidance decisions made by individual growth cones, we dye-filled the pCC interneuron, which normally extends an axon anteriorly along the ipsilateral longitudinal connective. In the presence of herbimycin A, the pCC growth cone was redirected across the anterior commissure. These phenotypes suggest that tyrosine kinase inhibition blocks a signaling mechanism that repels the growth cones of longitudinal connective neurons and prevents them from crossing the midline.


Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 671-682 ◽  
Author(s):  
B. Wightman ◽  
S.G. Clark ◽  
A.M. Taskar ◽  
W.C. Forrester ◽  
A.V. Maricq ◽  
...  

The assembly of the nervous system in the nematode C. elegans requires the directed migrations of cells and growth comes along the anteroposterior and dorsoventral body axis. We show here that the gene vab-8 is essential for most posteriorly directed migrations of cells and growth cones. Mutations in vab-8 disrupt fourteen of seventeen posteriorly directed migrations, but only two of seventeen anteriorly directed and dorsoventral migrations. For two types of neurons that extend axons both anteriorly and posteriorly, vab-8 mutations disrupt only the growth of the posteriorly directed axon. vab-8 encodes two genetic activities that function in the guidance of different migrations. Our results suggest that most posteriorly directed cell and growth cone migrations are guided by a common mechanism involving the vab-8 gene.


Development ◽  
1997 ◽  
Vol 124 (13) ◽  
pp. 2571-2580 ◽  
Author(s):  
B. Wightman ◽  
R. Baran ◽  
G. Garriga

During nervous system development, growth cone pioneering and fasciculation contribute to nerve bundle structure. Pioneer growth cones initially navigate along neuroglia to establish an axon scaffold that guides later extending growth cones. In C. elegans, the growth cone of the PVPR neuron pioneers the left ventral nerve cord bundle, providing a path for the embryonic extensions of the PVQL and AVKR growth cones. Later during larval development, the HSNL growth cone follows cues in the left ventral nerve cord bundle provided by the PVPR and PVQL axons. Here we show that mutations in the genes enu-1, fax-1, unc-3, unc-30, unc-42 and unc-115 disrupt pathfinding of growth cones along the left ventral nerve cord bundle. Our results indicate that unc-3 and unc-30 function in ventral nerve cord pioneering and that enu-1, fax-1, unc-42 and unc-115 function in recognition of the PVPR and PVQL axons by the AVKR and HSNL growth cones.


eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Huyen Nguyen ◽  
Peter Dayan ◽  
Zac Pujic ◽  
Justin Cooper-White ◽  
Geoffrey J Goodhill

Correct wiring is crucial for the proper functioning of the nervous system. Molecular gradients provide critical signals to guide growth cones, which are the motile tips of developing axons, to their targets. However, in vitro, growth cones trace highly stochastic trajectories, and exactly how molecular gradients bias their movement is unclear. Here, we introduce a mathematical model based on persistence, bias, and noise to describe this behaviour, constrained directly by measurements of the detailed statistics of growth cone movements in both attractive and repulsive gradients in a microfluidic device. This model provides a mathematical explanation for why average axon turning angles in gradients in vitro saturate very rapidly with time at relatively small values. This work introduces the most accurate predictive model of growth cone trajectories to date, and deepens our understanding of axon guidance events both in vitro and in vivo.


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