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B Fritzsch

Publications and source records attributed to B Fritzsch.

At least 55 records · Page 3Linked to original sources
PubMed1998

Evolution of the vestibulo-ocular system.

The evolutionary and developmental changes in the eye muscle innervation, the inner ear, and the vestibulo-ocular reflex are examined. Three eye muscle patterns, based on the innervation by distinct ocular motoneurons populations, can be identified: a lamprey, an elasmobranch, and a bony fish/tetrapod pattern. Four distinct patterns of variation in the vestibular system are described: a hagfish pattern, a lamprey pattern, an elasmobranch pattern, and a bony fish/tetrapod pattern. Developmental data suggest an influence of the hindbrain on ear pattern formation, thus potentially allowing a concomitant change of eye muscle innervation and ear variation. The connections between the ear and the vestibular nuclei and between the vestibular nuclei and ocular motoneurons are reviewed, and the role of neurotrophins for pattern specification is discussed. Three patterns are recognized in central projections: a hagfish pattern, a lamprey pattern, and a pattern for jawed vertebrates. Second-order connections show both similarities and differences between distantly related species such as lampreys and mammals. For example, elasmobranchs lack an internuclear system, which is at best poorly developed in lampreys. It is suggested that the vestibulo-ocular system shows only a limited degree of variation because of the pronounced functional constraints imposed on it.

Animals↗
PubMed1998

The combined effects of trkB and trkC mutations on the innervation of the inner ear.

Previous research has demonstrated that only the two neurotrophins and their cognate receptors are necessary for the support of the inner ear innervation. However, detailed analyses of patterns of innervation in various combinations of neurotrophin receptor mutants are lacking. We provide here such an analysis of the distribution of afferent and efferent fibers to the ear in various combinations of neurotrophin receptor mutants using the lipophilic tracer Dil. In the vestibular system, trkC+/- heterozygosity aggravates the trkB-/- mutation effect and causes almost complete loss of vestibular neurons. In the cochlea innervation, various mutations are each characterized by specific topological absence of spiral neurons in Rosenthal's canal of the cochlea. trkC-/- mutation alone or in combination with trkB+/- heterozygosity causes absence of all basal turn spiral neurons and afferent fibers extend from the middle turn to the basal turn along inner hair cells with little or no contribution to outer hair cells. Both types of basal turn spiral neurons appear to develop and project via radial fibers to inner and, more sparingly, outer hair cells. Simple trkB-/- mutations show a reduction of fibers to outer hair cells in the apex and, less obvious, in the basal turn. Basal turn spiral neurons may be the only neurons present at birth in the cochlea of a trkB-/- mutant mouse combined with trkC+/- heterozygosity. In addition, the trkB-/- mutation combined with trkC+/- heterozygosity has a patchy and variable loss of middle turn spiral neurons in mice of different litters. Comparisons of patterns of innervation of afferent and efferent fibers show a striking similarity of absence of fibers to topologically corresponding areas. For example, in trkC-/- mutants afferents reach the basal turn, spiraling along the cochlea, rather than through radial fibers and efferent fibers follow the same pathway rather than emanating from intraganglionic spiral fibers. The data presented suggest that there are regional specific effects with some bias towards a specific spiral ganglion type: trkC is essential for support of basal turn spiral neurons whereas trkB appears to be more important for middle and apical turn spiral neurons.

Animals↗
PubMed1998

Of mice and genes: evolution of vertebrate brain development.

In this review the current understanding of genetic and molecular evolution of development, in particular the formation of the major axis of bilateral animals, is critically evaluated, and the early pattern formation in the hindbrain is related as much as possible to these processes. On the genetic level it is proposed that the exuberant multiplication of regulatory genes compared to that of structural genes relates to the increased flexibility of early vertebrate development. In comparisons to fruit flies, many conserved genes are found to be expressed very differently, while many others seem to reflect a comparable pattern and thus suggest a conservation of function. Even genes with a largely conserved pattern of expression may change the level at which they are expressed and the mechanisms by which they are regulated in their expression. Evolution and development of hindbrain motoneurons is reviewed, and it is concluded that both comparative data as well as more recent experimental data suggest a limited importance for the rhombomeres. Clearly, many cell fate-specifying processes work below the level of rhombomeres or in the absence of rhombomeres. It is suggested that more comparative developmental data are needed to establish firmly the relationship between homeobox genes and rhombomere specification in vertebrates other than a few model species.

Animals↗
PubMed1998

A mechanism for anterior transposition of the anal fin and its appendicular support in the western mosquitofish, gambusia affinis affinis

The interosseal and suspensory ligaments of the axial and appendicular skeleton of the Western Mosquitofish, Gambusia affinis affinis were investigated in whole-mounted late embryonic and adult female and male G. a. affinis stained with alcian blue and alizarin red S, cleared, and viewed using differential interference contrast. The interosseal and suspensory ligaments of late embryonic female G. a. affinis are reduced prior to sexual differentiation and continue reduced in adult females. However, in late embryonic male G. a. affinis the interosseal and suspensory ligaments are well developed prior to sexual differentiation and become robust in adult males. Treating late embryonic female G. a. affinis with either 30.0 or 40. 0 &mgr;g/ diet of 17alpha-methyltestosterone led to the premature calcification of the hemal spine of the 13th vertebra. Treating late embryonic female G. a. affinis with 17alpha-methyltestosterone did not lead to the remodeling of the hemal spines of the 14th-16th vertebrae. Thus, in all female G. a. affinis treated with 17alpha-methyltestosterone, no anterior transposition of the anal fin and its appendicular support was observed. However, treating late embryonic male G. a. affinis with 30.0 &mgr;g/g diet of 17alpha-methyltestosterone led to the premature calcification of the hemal spine of the 13th vertebra, blocking the anterior transposition in only 62.5% of the males treated, and treating late embryonic male G. a. affinis with 40.0 &mgr;g/g diet of 17alpha-methyltestosterone led to the premature calcification of the hemal spine of the 13th vertebra, blocking the anterior transposition in all (100.0%) males treated. Treatment with either 30.0 or 40.0 &mgr;g/g diet of 17alpha-methyltestosterone appeared not to completely effect the interosseal and suspensory ligaments of late embryonic male G.a. affinis as evident by the male-specific remodeling of the hemal spines of the 14th-16th vertebrae. The results of this study implicate the interosseal and suspensory ligaments in the male-specific remodeling of the axial and appendicular skeletal elements. Following the resorption of the 13th hemal spine, the interosseal and suspensory ligaments in late embryonic male G. a. affinis develop enough tension to cause directional growth, bending, and elongation of the 14th-16th hemal spines, thus providing a mechanism for the anterior transposition of the sexually dimorphic anal fin and its appendicular support. The data also support the need to revise the interosseal and suspensory ligament nomenclature by assigning the designation of 'female' and 'male' to these ligaments.

Journal Article↗
PubMed1997

Lack of neurotrophin 3 causes losses of both classes of spiral ganglion neurons in the cochlea in a region-specific fashion.

Essential functions of neurotrophin 3 (NT-3) in regulating afferent and efferent innervation of the cochlea have been characterized by comparison of normal and NT-3 mutant mice. NT-3 deficiency has striking, region-specific effects, with complete loss of sensory neurons in the basal turn and dramatic but incomplete neuronal loss in the middle and apical turns. The sensory innervation of inner and outer hair cells was reorganized in mutant animals. Instead of a strictly radial pattern of innervation, the axons of remaining sensory neurons projected spirally along the row of inner hair cells to innervate even the most basal inner hair cells. Innervation of outer hair cells was strongly reduced overall and was not detected in the basal turn. The presence of fibers extending to both inner and outer hair cells suggests that subsets of types I and II sensory neurons survive in the absence of NT-3. Likewise, projections of the cochlea to auditory nuclei of the brainstem were attenuated but otherwise present. Equally striking changes in efferent innervation were observed in mutant animals that closely mimicked the abnormal sensory innervation pattern. Despite these impressive innervation deficiencies, the morphology of the organ of Corti and the development of inner and outer hair cells appeared comparatively normal.

Animals↗
PubMed1997

Electron microscopic differentiation of directly and transneuronally transported DiI and applications for studies of synaptogenesis.

The neuronal tracer DiI is a lipophilic dye which diffuses along the lipid bilayer of membranes and sometimes will move transcellularly. We used this tracer to study the development of olivocochlear synapses in the auditory system in rats and chickens by applying DiI directly to severed axons in the olivocochlear bundle. Observations with epi-fluorescent microscopy showed that DiI had labelled efferent axons directly and had labelled spiral ganglion cells and hair cells transneuronally. Ultrastructural analysis of photoconverted DiI tissue in rats revealed that transneuronal diffusion occurred when the plasma membrane of directly labelled axons made contact with the plasma membrane of their target structure. Directly and transneuronally labelled profiles can be distinguished easily at the electron microscopic level. In directly labelled profiles, all plasma, nuclear, endoplasmic reticulum, and outer mitochondrial membranes and cell cytoplasm are labelled leaving only the mitochondrial matrix unstained. However, in transneuronally labelled cells the endoplasmic, nuclear, and immature synaptic membranes are labelled but mitochondrial and non-synaptic plasma membranes are not labelled. This labelling pattern can be explained by diffusion through continuous membranes. These characteristics make DiI diffusion a powerful technique for identifying and studying early events in neuronal development and synapse formation.

Animals↗
PubMed1997

Effects of neurotrophin and neurotrophin receptor disruption on the afferent inner ear innervation.

Two neurotrophins and their two receptors appear to regulate the survival of vestibular and cochlear neurons in the developing ear. Mice lacking either brain derived neurotrophic factor (BDNF) or its associated receptor, Trk B, show a severe reduction in the number of vestibular neurons and a loss of all innervation to the semicircular canals. Mice lacking NT-3 or its receptor, Trk C, show a severe reduction of spiral neurons in the basal turn of the cochlea. Mice lacking both BDNF and NT-3 or Trk B and Trk C, reportedly lose all innervation to the inner ear. These two neurotrophins and their associated receptors are necessary for the normal afferent innervation of the inner ear.

Journal Article↗
PubMed1997

Sex differences in endogenous retinoid release in the post-embryonic spinal cord of the western mosquitofish, Gambusia affinis affinis.

In this study we have shown sex differences in endogenous retinoic acid synthesis and retinaldehyde dehydrogenase activity in the post-embryonic spinal cords of immature female and male G. a. affinis. The F9 reporter cell assay and the zymography bioassay showed that the endogenous retinoic acid levels correlated with the levels of the endogenous enzyme(s) responsible for retinoic acid synthesis. These data also showed that both the endogenous retinoic acid levels and the enzyme(s) were higher in spinal cord segments 8-16 of immature males than in immature females. We have also shown that exogenous treatment of 17 alpha-methyltestosterone results in the masculinization of the immature female's anal fin and its appendicular support elements as well as the endogenous synthesis of retinoic acid and retinaldehyde dehydrogenase activity. The F9 reporter cell assay showed that the endogenous retinoic acid levels were relatively unchanged in spinal cord segments 8-16 of immature males treated with 17 alpha-methyltestosterone. However, the F9 reporter cell assay showed that the endogenous retinoic acid levels in spinal cord segments 8-16 of immature females treated with 17 alpha-methyltestosterone were markedly higher than levels observed in the immature males. The data also showed that the activity of the enzyme(s) responsible for the synthesis of endogenous retinoic acid was higher in spinal cord segments 8-16 of immature females treated with 17 alpha-methyltestosterone than in immature males treated with 17 alpha-methyltestosterone. Currently under investigation is the question of what role the endogenous enzyme(s) responsible for the synthesis of retinoic acid plays either alone or in concert with androgen in organizing hormone-dependent sexually dimorphic areas in the teleost body plan.

Aging↗
PubMed1997

The role of neurotrophic factors in regulating the development of inner ear innervation.

Several neurotrophins and their receptors regulate the survival of vestibular and cochlear neurons and probably also the efferent and autonomic neurons that innervate the inner ear. Mice lacking either brain-derived neurotrophic factor (BDNF) or its associated receptor, TrkB, lose all innervation to the semicircular canals and have reduced innervation of the outer hair cells in the apical and middle turns of the cochlea. Mice lacking neurotrophin-3 (NT-3) or its receptor, TrkC, lose many spiral ganglion cells predominantly in the basal turn of the cochlea. Nerve fibers from spiral ganglion cells in the middle turn extended to inner hair cells of the base. In mice lacking both BDNF and NT-3, or both TrkB and TrkC, there is a complete loss of innervation to the inner ear. Thus, these two neurotrophins and their associated receptors have been shown to be absolutely necessary for the normal development of afferent innervation of the inner ear. Current research efforts are testing the therapeutic potential for neurotrophins to treat hearing loss.

Animals↗
PubMed1997

Mice with a targeted disruption of the neurotrophin receptor trkB lose their gustatory ganglion cells early but do develop taste buds.

The alleged ability of taste afferents to induce taste buds in developing animals is investigated using a mouse model with a targeted deletion of the tyrosine kinase receptor trkB for the neurotrophin BDNF. This neurotrophin was recently shown to be expressed in developing taste buds and the receptor trkB has been shown to be expressed in the developing ganglion cells that innervate the taste buds. Our data show a reduction of geniculate ganglion cells to about 5% of control animals in neonates. Degeneration of ganglion cells starts when processes reach the central target (solitary tract) but before they reach the peripheral target (taste buds). Degeneration of ganglion cells is almost completed in trkB knockout mice before taste afferents reach in control animals the developing fungiform papillae. Four days later the first taste buds can be identified in fungiform papillae of both control and trkB knockout mice in about equal number and density. Many taste buds undergo a normal maturation compared to control animals. However, the more lateral and caudal fungiform papillae grow less in size and become less conspicuous in older trkB knockout mice. No intragemmal innervation can be found in trkB knockout taste buds but a few extragemmal fibers enter the apex and end between taste had cells without forming specialized synapses. Taste buds of trkB knockout mice appear less well organized than those of control mice, but some cells show similar vesicle accumulations as control taste bud cells in their base but no synaptic contact to an afferent. These data strongly suggest that the initial-development of many fungiform papillae and taste buds is independent of the specific taste innervation. It remains to be shown why others appear to be more dependent on proper innervation.

Animals↗
PubMed1997

The development of vestibulocochlear efferents and cochlear afferents in mice.

We have reinvestigated the embryonic development of the vestibulocochlear system in mice using anterograde and retrograde tracing techniques. Our studies reveal that rhombomeres 4 and 5 include five motor neuron populations. One of these, the abducens nucleus, will not be dealt with here. Rhombomere 4 gives rise to three of the remaining populations: the facial branchial motor neurons; the vestibular efferents; and the cochlear efferents. The migration of the facial branchial motor neurons away from the otic efferents is completed by 13.5 days post coitum (dpc). Subsequently the otic efferents separate into the vestibular and cochlear efferents, and complete their migration by 14.5 dpc. In addition to their common origin, all three populations have perikarya that migrate via translocation through secondary processes, form a continuous column upon completion of their migrations, and form axonal tracts that run in the internal facial genu. Some otic efferent axons travel with the facial branchial motor nerve from the internal facial genu and exit the brain with that nerve. These data suggest that facial branchial motor neurons and otic efferents are derived from a common precursor population and use similar cues for pathway recognition within the brain. In contrast, rhombomere 5 gives rise to the fourth population to be considered here, the superior salivatory nucleus, a visceral motor neuron group. Other differences between this group and those derived from rhombomere 4 include perikaryal migration as a result of translocation first through primary processes and only then through secondary processes, a final location lateral to the branchial motor/otic efferent column, and axonal tracts that are completely segregated from those of the facial branchial and otic efferents throughout their course inside the brain. Analysis of the peripheral distribution of the cochlear efferents and afferents show that efferents reach the spiral ganglion at 12.5 dpc when postmitotic ganglion cells are migrating away from the cochlear anlage. The efferents begin to form the intraganglionic spiral bundle by 14.5 dpc and the inner spiral bundle by 16.5 dpc in the basal turn. They have extensive collaterals among supporting cells of the greater epithelial ridge from 16.5 dpc onwards. Afferents and efferents in the basal turn of the cochlea extend through all three rows of outer hair cells by 18.5 dpc. Selective labeling of afferent fibers at 20.5 dpc (postnatal day 1) shows that although some afferents are still in early developmental stages, some type II spiral ganglion cells already extend for long distances along the outer hair cells, and some type I spiral ganglion cells end on a single inner hair cell. These data support previous evidence that in mice the early outgrowth of afferent and efferent fibers is essentially achieved by birth.

Animals↗
PubMed1997

Severe sensory deficits but normal CNS development in newborn mice lacking TrkB and TrkC tyrosine protein kinase receptors.

Analysis of mice carrying targeted mutations in genes encoding neurotrophins and their signalling Trk receptors has provided critical information regarding the role that these molecules play in the mammalian nervous system. In this study we generated mice defective in both TrkB and TrkC tyrosine kinase receptors to determine the biological effects of these receptors in the absence of compensatory mechanisms. trkB(-/-);trkC(-/-) double-mutant mice were born at the expected frequency, indicating that TrkB and TrkC signalling are not required for embryonic survival. However, these double-mutant mice had a significantly shorter lifespan and displayed more severe sensory defects than their single-mutant trkB(-/-) and trkC(-/-) littermates. The most dramatic sensory deficit observed in trkB(-/-);trkC(-/-) mutant mice was the absence of vestibular and cochlear ganglia. Interestingly, these mice developed inner ear sensory epithelia in spite of the complete absence of sensory innervation. Analysis of the CNS in trkB(-/-);trkC(-/-) mutant mice revealed a well formed hippocampus, cortex and thalamus. Moreover, the pattern of expression of several neuronal markers appeared normal in these animals. These observations suggest that neurotrophin signalling through TrkB and TrkC receptors is essential for the development of sensory ganglia; however, it does not play a major role in the differentiation and survival of CNS neurons during embryonic development.

Animals↗
PubMed1997

On the role played by ontogenetic remodeling and functional transformation in the evolution of terrestrial hearing.

Using examples from the octavolateral system, evidence is reviewed suggesting a relationship between regressive events, such as loss of one function, or loss of one sensory subsystem, and progressive evolutionary changes in topologically associated systems. While none of the neuronal examples in the evolutionary reorganization of the otic region are as clear-cut as the initial example of non-neuronal reorganization on which the correlation of regressive with progressive changes is based (the functional transformation of the hyomandibular bone into the stapes), the general principle that a chance correlation of two insignificant events may lead to a novel function may be valid for more aspects of the evolution of the ear, in particular the auditory system, than is currently appreciated. It is suggested that regressive events may not only be an evolutionary dead end but that they may provide, through the relaxation of constraints imposed on the respective structure, a source for innovations. However, transformations of functionally uncoupled structures into a novel adaptive function will occur only when topologically adjacent structures require these transformations to improve their own function.

Animals↗
PubMed1997

Evidence that FGF8 signalling from the midbrain-hindbrain junction regulates growth and polarity in the developing midbrain.

The developing vertebrate mesencephalon shows a rostrocaudal gradient in the expression of a number of molecular markers and in the cytoarchitectonic differentiation of the tectum, where cells cease proliferating and differentiate in a rostral to caudal progression. Tissue grafting experiments have implicated cell signalling by the mesencephalic-metencephalic (mid-hindbrain) junction (or isthmus) in orchestrating these events. We have explored the role of Wnt-1 and FGF8 signalling in the regulation of mesencephalic polarity. Wnt-1 is expressed in the caudal mesencephalon and Fgf8 in the most rostral metencephalon. Wnt-1 regulates Fgf8 expression in the adjacent metencephalon, most likely via a secondary mesencephalic signal. Ectopic expression of Fgf8 in the mesencephalon is sufficient to activate expression of Engrailed-2 (En-2) and ELF-1, two genes normally expressed in a decreasing caudal to rostral gradient in the posterior mesencephalon. Ectopic expression of Engrailed-1 (En-1), a functionally equivalent homologue of En-2 is sufficient to activate ELF-1 expression by itself. These results indicate the existence of a molecular hierarchy in which FGF8 signalling establishes the graded expression of En-2 within the tectum. This in turn may act to specify other aspects of A-P polarity such as graded ELF-1 expression. Our studies also reveal that FGF8 is a potent mitogen within the mesencephalon: when ectopically expressed, neural precursors continue to proliferate and neurogenesis is prevented. Taken together our results suggest that FGF8 signalling from the isthmus has a key role in coordinately regulating growth and polarity in the developing mesencephalon.

Animals↗
PubMed1997

The development of vestibular connections in rat embryos in microgravity.

Existing experimental embryological data suggests that the vestibular system initially develops in a very rigid and genetically controlled manner. Nevertheless, gravity appears to be a critical factor in the normal development of the vestibular system that monitors position with respect to gravity (saccule and utricle). In fact several studies have shown that prenatal exposure to microgravity causes temporary deficits in gravity-dependent righting behaviors, and prolonged exposure to hypergravity from conception to weaning causes permanent deficits in gravity-dependent righting behaviors. Data on hypergravity and microgravity exposure suggest some changes in the otolith formation during development, in particular the size although these changes may actually vary with the species involved. In adults exposed to microgravity there is a change in the synaptic density in the optic sensory epithelia suggesting that some adaptation may occur there. However, effects have also been reported in the brainstem. Several studies have shown synaptic changes in the lateral vestibular nucleus and in the nodulus of the cerebellum after neonatal exposure to hypergravity. We report here that synaptogenesis in the medial vestibular nucleus is retarded in developing rat embryos that were exposed to microgravity from gestation days 9 to 19.

Animals↗
PubMed1997

Effects of neurotrophin and neurotrophin receptor disruption on the afferent inner ear innervation.

Two neurotrophins and their two receptors appear to regulate the survival of vestibular and cochlear neurons in the developing ear. Mice lacking either brain derived neurotrophic factor (BDNF) or its associated receptor, Trk B, show a severe reduction in the number of vestibular neurons and a loss of all innervation to the semicircular canals. Mice lacking NT-3 or its receptor, Trk C, show a severe reduction of spiral neurons in the basal turn of the cochlea. Mice lacking both BDNF and NT-3 or Trk B and Trk C, reportedly lose all innervation to the inner ear. These two neurotrophins and their associated receptors are necessary for the normal afferent innervation of the inner ear.

Animals↗
PubMed1997

Distribution of BDNF and trkB mRNA in the otic region of 3.5 and 4.5 day chick embryos as revealed with a combination of in situ hybridization and tract tracing.

We have used a recently developed technique which combines fluorescent tract tracing and in situ hybridization to study co-localization of neurotrophin mRNA and neurotrophin receptor mRNA expression simultaneously with the pattern of innervation in the developing chick ear. Efferent and afferent fibersfrom the VII/VIIIth cranial nerves were retrogradely and anterogradely filled with Dextran amines conjugated to Texas red and the brain stem was incubated for 2 hours in tissue culture medium. The tissue was subsequently fixed, sectioned frozen, mounted and subjected to in situ hybridization analysis using probes for brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor, trkB. The results show that afferent and efferent fibers to the ear innervate areas of the developing otocyst which express BDNF mRNA. We also found that neurons in the stato-acoustic ganglion express high levels of trkB mRNA whereas the subset of facial motor neurons that is efferent to the ear only had no or very low levels of trkB mRNA. From our results we conclude that chicken otic efferent fibers preferentially project to areas with BDNF mRNA expression. The very low levels of trkB mRNA in these motor neurons compared to afferent neurons innervating the same region suggest that other factors, perhaps co-expressed with BDNF, may support efferents. A possible involvement of afferents in guiding efferents to specific areas of the ear is suggested.

Animals↗