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Biomedical subjects

M J Katz

Publications and source records attributed to M J Katz.

At least 37 records · Page 2Linked to original sources

Axonal branch shapes.

To distinguish the relative roles of the intrinsic and the extrinsic determinants of axonal branching shapes, a number of key branch parameters were measured under a variety of conditions. Branch shapes of frog and of chick axons were analyzed in tissue culture, and these in vitro patterns were compared with in vivo branch patterns of axons in tadpole tail fins. The shape of a branch junction can be characterized by the sizes of its branch angles. In all cases, branch junctions had only two branches (3 branch angles), and the bifurcation angle between them was usually the smallest. The shape of the branch junction was constant in a wide variety of environments, but the exact branch angles, as well as the numbers of branches per axon and the numbers of axons per neuron, could be modulated by changes in the substrate adhesivity.

Animals↗

Templeting and self-assembly.

Templeting and self-assembly represent the two extremes of the spectrum of determinate pattern-assembly processes. A templeted pattern can be defined as one that requires a prepattern or templet explicitly specifying the final topology of the pattern. Conversely, a self-assembling pattern can be defined as one for which the inherent constraints of the precursor elements alone are sufficient to specify the final pattern. Both concepts can be directly expressed in matrix notation, and a simple matrix measure, the templeting index, characterizes the relative amount of templeting or of self-assembly in any particular system. With this language, a fundamental principle of pattern-assembly becomes evident: in the determinate realm, some patterns can only be assembled using the same-sized templets--templets that are at least as large as the final pattern.

Mathematics↗

Early axon patterns of the spinal cord: experiments with a computer.

In the vertebrate central nervous system, most axons appear in one of two elemental patterns--sheets or bundles. Many developmental mechanisms are involved in the formation of the elemental axon patterns, and these mechanisms often act simultaneously. The major axon-patterning mechanisms include differential adhesivity, internal growth constraints on axons, and initial orientation of axonal outgrowth. To evaluate the effects of these mechanisms on the formation of axon patterns, a computer was used to model axonal growth. Experiments with the computer model suggest that axon sheets are produced by the cooperative action of more than one mechanism. Furthermore, in the appropriate combination, these mechanisms produce orderly axon sheets even on patternless substrates. On the other hand, to transform the sheets into axon bundles, the substrate must be patterned.

Animals↗

Prevention and treatment of sciatic denervation disuse osteoporosis in the rat tibia with capacitively coupled electrical stimulation.

Osteoporosis in the sciatic-denervated rat tibia was both prevented and reversed with a capacitively coupled electrical field. In both the prevention of the development of osteoporosis and the reversal of a previously established osteoporosis, a statistically significant enhancement of wet weight, dry weight, ashed weight, ultimate strength, cortical area, cortical thickness, and a concomitant decrease in cortical porosity occurred in the stimulated, denervated tibiae of the experimental animals compared with the nonstimulated, denervated tibiae of the control animals. These effects exhibited dose-response characteristics. A 60 kHz symmetrical sinewave signal was effective in preventing osteoporosis at a range of 5-10 peak-to-peak, and it was effective in reversing osteoporosis at 10 V peak-to-peak. Reversal of a well-established osteoporosis in laboratory animals has not been reported previously. Continued investigation into the use of a capacitively coupled electrical field in the prevention and treatment of osteoporosis seems warranted from these studies.

Animals↗

Intensifier for Bodian staining of tissue sections and cell cultures.

Intensification of the standard Bodian silver stain with a poststaining photographic enhancer produces high resolution of fine cell processes such as axonal growth cones. This technique can be used on tissue sections and is especially useful for visualizing individual cells fixed in tissue cultures.

Animals↗

How straight do axons grow?

Detailed growth paths of embryonic frog and chick axons were measured as the axons elongated in dispersed cultures on acid-rinsed glass surfaces. Mathematical analyses demonstrate that, under these conditions, axons do not grow randomly but tend to grow straight. Growth cones appear to actively alternate sides--right and left from the straight line of growth--and the growth cone neck exhibits all possible angles, but the axon itself maintains a fairly constant orientation. It appears that an axonal resistance to bending may be the cause of the intrinsic tendency for relatively straight axonal growth. The natural straightness of axonal growth may be an important developmental determinant of certain in vivo axon patterns.

Animals↗

Axonal elongation as a stochastic walk.

A new formula calculates rates of directed axonal growth (elongation or retraction) using measurements of growth cone movements. By explicitly separating changes in axonal length from other nonelongational growth cone movements, the calculated rates reflect the detailed cellular growth mechanisms more directly than previous growth measures. In addition, the formula produces three distinct parameters of axonal elongation: n, a growth step rate; s, a growth step size; and P, a probability that a growth step leads to axonal elongation. For normal and regenerating individual chick and frog axons in culture, the formula has quantitated the following differences: the axon itself can elongate more rapidly in the chick, and the axon elongates in smaller steps in the chick. The underlying dynamics of growth of regenerating axons are quite similar to normal axons, but, in the short term, regenerating axons elongate in larger steps and at a slower rate. The distribution of these new rate measurements suggests that the elongation of axons can be usefully modelled as a one-dimensional stochastic walk.

Animals↗

Stereotyped and variable growth of redirected Mauthner axons.

To assay the axon tract organizing capabilities of different regions of the vertebrate CNS, Mauthner axons were redirected by grafting supernumerary hindbrains in Xenopus embryos. The 63 redirected Mauthner axons thus produced included donor axons projecting into the host CNS and host axons that grew through the graft or that were redirected in the host CNS. Two major phenomena were observed. Caudal to the optic chiasm, the Mauthner axons followed a single ipsilateral stereotyped route--the basal substrate pathway--extending in the ventral and ventrolateral marginal zone from the diencephalon to the caudal spinal cord. In contrast, rostral to the optic chiasm, these same Mauthner axons followed variable ipsilateral and contralateral routes. Even pairs of Mauthner axons entering the optic chiasm side-by-side eventually followed different routes in normal forebrains. The contrasting behaviors of the Mauthner axons growing in the rostral diencephalon and telencephalon and of the same Mauthner axons growing elsewhere suggest that there are differences in the effective guidance cues between these two regions of the developing brain. This is consistent with other types of neuroanatomical and neuroembryological evidence indicating a fundamental division between the rostral and the caudal diencephalon.

Animals↗

CNS effects of mechanically produced spina bifida.

Neural-tube defects were produced by one of two mechanical perturbations in an amphibian model system: newly-formed neural tubes were slit dorsally, or an intrinsic mass (an eye primordium transplanted to the neural plate) was introduced to prevent dorsal closure. Electron microscopic analyses showed that the resulting CNS distortions invariably included paired spinal-cord tubes that developed ciliated central canals surrounded by cellular layers and rimmed laterally by axon-filled marginal zones. Specific axon tracts grew in appropriate locations through the regions of simple diastematomyelia. Even in the most histologically distorted regions, ventral roots developed, axons were myelinated, and neuromuscular synapses formed in adjacent muscles. On the other hand, an excess of cells populated the defects and in histologically distorted regions the axon tracts were clearly less well organized than in normal animals. Neural-crest cells and the notochord did not appear to be affected. In addition, distant neurons and axon tracts appeared normal. These mechanical lesions could produce spina bifida without hydrocephalus. It is concluded that mechanical lesions to the forming neural tube will produce mainly local effects with a strong tendency toward diastematomyelia.

Animals↗

Ontophyletics of the nervous system: development of the corpus callosum and evolution of axon tracts.

The evolution of nervous systems has included significant changes in the axon tracts of the central nervous system. These evolutionary changes required changes in axonal growth in embryos. During development, many axons reach their targets by following guidance cues that are organized as pathways in the embryonic substrate, and the overall pattern of the major axon tracts in the adult can be traced back to the fundamental pattern of such substrate pathways. Embryological and comparative anatomical studies suggest that most axon tracts, such as the anterior commissure, have evolved by the modified use of preexisting substrate pathways. On the other hand, recent developmental studies suggest that a few entirely new substrate pathways have arisen during evolution; these apparently provided opportunities for the formation of completely new axon tracts. The corpus callosum, which is found only in placental mammals, may be such a truly new axon tract. We propose that the evolution of the corpus callosum is founded on the emergence of a new preaxonal substrate pathway, the "glial sling," which bridges the two halves of the embryonic forebrain only in placental mammals.

Animals↗

Substrate pathways demonstrated by transplanted Mauthner axons.

A substrate pathway is a set of aligned guidance cues. (Such cues may be either cells or molecules.) CNS substrate pathways can be demonstrated by transplanting axons to different starting locations. The stereotyped routes of transplanted axons will then demonstrate the locations of effective substrate pathways. To map CNS substrate pathways, Mauthner axons were transplanted to various unnatural locations along the CNS of Xenopus embryos. The routes of 24 experimental Mauthner axons were traced. Twenty-one of these axons grew along parts of a stereotyped route extending in the ventral marginal zone from the caudal diencephalon through the spinal cord. This ventral substrate pathway ran the length of the basal plate; thus, we call it a basal substrate pathway. One experimental Mauthner axon grew along the alar substrate pathway previously demonstrated by transplanted optic axons. The demonstrations of the alar and the basal substrate pathways suggest that during development a few long substrate pathways organize the overall layout of the long tracts of the CNS. We propose that the pattern of the earliest CNS substrate pathways is established in the neural plate and is topologically preserved as the neural plate rolls into a neural tube. This pattern may be manifest as the three-dimensional organization of the early marginal zones formed by the peripheral processes (the endfeet) of certain developing ependyma and radial glia. Subsequently, the detailed anatomy of the axon tracts and the specific terminations of individual axons are probably determined by other local chemical cues.

Brain↗

Ontophyletics of the nervous system: eyeless mutants illustrate how ontogenetic buffer mechanisms channel evolution.

Genetics and molecular biology have shown the mechanisms that allow the genome to provide both the continuity and the variation from generation to generation within a phylogeny. Embryology and developmental biology show the mechanisms that turn the genome into an organism. Mutations, the basis for evolutionary change, cannot in themselves ensure concordance between their products and the products of unchanged genes. Thus, mutations will not necessarily produce a viable organism. On the other hand, ontogenetic buffer mechanisms normally maintain concordance in the developing organism. In addition, ontogenetic buffer mechanisms can integrate discordant mutations into viable organisms that can then be perpetuated during evolution. The evolutionary role of one ontogenetic buffer mechanism, compensatory innervation, is well illustrated in the anopthalmic mutant mouse. In the anopthalmic mouse, a single gene mutation removes afferent axons of the dorsal lateral geniculate nucleus, and compensatory innervation by another population of axons ensures that the dorsal lateral geniculate remains integrated into the central nervous system. Within each organism's ontogeny is a hierarchy of sources of compensatory innervation, and this hierarchy will determine how any particular deafferentating mutation will be buffered. In this way, an ontogeny can channel the phylogeny of which it is a member.

Animals↗

Invited review: guidance cue patterns and cell migration in multicellular organisms.

In multicellular organisms, guidance cues are either diffusible molecules or cellular or extracellular surfaces that are found in reproducible locations and that orient migrating cells and cell processes. The pattern of the guidance cues usually determines the complex in vivo migration routes of motile cells and cell processes. Within organisms, guidance cues are found to be organized in two general patterns: a) broad gradients--such as diffuse chemotactic gradients; b) discrete routes (substrate pathways)--such as chemotactic gradients confined to long channels, and such as the axon surface which represents a long specific highway for migrating Schwann cells.

Amphibians↗