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Biomedical subjects

G Schlosser

Publications and source records attributed to G Schlosser.

16 recordsLinked to original sources

Limb development in a "nonmodel" vertebrate, the direct-developing frog Eleutherodactylus coqui.

Mechanisms that mediate limb development are regarded as highly conserved among vertebrates, especially tetrapods. Yet, this assumption is based on the study of relatively few species, and virtually none of those that display any of a large number of specialized life-history or reproductive modes, which might be expected to affect developmental pattern or process. Direct development is an alternative life history found in many anuran amphibians. Many adult features that form after hatching in metamorphic frogs, such as limbs, appear during embryogenesis in direct-developing species. Limb development in the direct-developing frog Eleutherodactylus coqui presents a mosaic of apparently conserved and novel features. The former include the basic sequence and pattern of limb chondrogenesis, which are typical of anurans generally and appear largely unaffected by the gross shift in developmental timing; expression of Distal-less protein (Dlx) in the distal ectoderm; expression of the gene Sonic hedgehog (Shh) in the zone of polarizing activity (ZPA); and the ability of the ZPA to induce supernumerary digits when transplanted to the anterior region of an early host limb bud. Novel features include the absence of a morphologically distinct apical ectodermal ridge, the ability of the limb to continue distal outgrowth and differentiation following removal of the distal ectoderm, and earlier cessation of the inductive ability of the ZPA. Attempts to represent tetrapod limb development as a developmental "module" must allow for this kind of evolutionary variation among species.

Animals↗

Using heterochrony plots to detect the dissociated coevolution of characters.

The comparison of developmental sequences among species is notoriously difficult. Here, heterochrony plots are introduced as a new graphic method to detect temporal shifts in the development of characters in pair-wise species comparisons. Plotting the timing of character development in one species against the timing of character development in another species allows us to compare a principally unlimited number of characters simultaneously and can detect whether suites of characters are dissociated from one another or not. Such heterochrony plots can be embedded into a comparative phylogenetic analysis in order to establish whether observed patterns of character codissociation are indeed due to their dissociated coevolution. Comparative phylogenetic analysis may also reveal multiple independent events of dissociated coevolution of the same suite of characters in a certain lineage, suggesting that the characters of this suite reciprocally constrain their evolutionary modifiability, thereby forming a unit of evolution. This ability to identify units of evolution is a prerequisite for assessing the validity of recently proposed scenarios, suggesting that modules of development and/or function tend to act as units of evolution. Starting from a detailed heterochrony plot comparing development in the direct developing frog Eleutherodactylus coqui and in the biphasically developing frog Discoglossus pictus, this comparative approach is illustrated focusing on the evolution of development of limbs, the nervous system and the pharyngeal arches in amphibians.

Amphibians↗

Lateral line placodes are induced during neurulation in the axolotl.

In order to determine the time window for induction of lateral line placodes in the axolotl, we performed two series of heterotopic and isochronic transplantations from pigmented to albino embryos at different stages of embryogenesis and assessed the distribution of pigmented neuromasts in the hosts at later stages. First, ectoderm from the prospective placodal region was transplanted to the belly between early neurula and mid tailbud stages (stages 13-27). Whereas grafts from early neurulae typically differentiated only into epidermis, grafts from late neural fold stages on reliably resulted in differentiation of ectopic pigmented neuromasts. Second, belly ectoderm was transplanted to the prospective placodal region between early neurula and tailbud stages (stages 13-35). Normal lateral lines containing pigmented neuromasts formed in most embryos when grafts were performed prior to early tailbud stages (stage 24) but not when they were performed later. Our findings indicate that lateral line placodes, from which neuromasts originate, are already determined at late neural fold stages (first series of grafts) but are inducible until early tailbud stages (second series of grafts). A further series of heterochronic transplantations demonstrated that the decline of inducibility at mid tailbud stages is mainly due to the loss of ectodermal competence.

Abdomen↗

Xenopus Eya1 demarcates all neurogenic placodes as well as migrating hypaxial muscle precursors.

We cloned two isoforms of the Xenopus Eya1 orthologue. They show identical patterns of expression that closely resemble the previously described expression of XSix1, but partly differ from the expression of Eya1 in other vertebrates. XEya1 is expressed in the somites and hypaxial muscle precursors, but not in the pronephros. Moreover, all ectodermal placodes except the lens placode strongly express XEya1. At neural plate stages, ectodermal XEya1 expression starts in two domains, the anterior neural folds and a domain lateral to the neural folds. At tailbud stages, XEya1 expression continues in the adenohypophysis, all neurogenic placodes and placodally-derived structures including cranial ganglia, the otic vesicle and lateral line primordia.

Amino Acid Sequence↗

Development of neurogenic placodes in Xenopus laevis.

The development of neurogenic placodes in Xenopus laevis from the time of neural fold closure to larval stages is described. Placodes were reconstructed from camera lucida drawings of serial sections, and the spatiotemporal pattern of placodal neurogenesis was analyzed using in situ hybridization for the genes X-NGNR-1, XNeuroD, X-MyT1, and X-Delta-1, all of which have been implicated in the regulation of neurogenesis. Olfactory, profundal, and trigeminal placodes, a series of dorsolateral placodes (otic placode and five lateral line placodes), a series of epibranchial placodes, and two hypobranchial placodes were identified. Earlier claims that all placodes in anurans develop from a common primordium could not be confirmed. Profundal and trigeminal placodes, however, are partially fused, and all lateral line placodes arise from a common precursor. Epibranchial and hypobranchial placodes develop ventral to other placodes and dorsal and ventral to the pharyngeal pouches, respectively. Hypobranchial placodes give rise to neurons that become intimately associated with the developing heart. All neurogenic placodes strongly express the neuronal differentiation gene XNeuroD. The neuronal determination gene X-NGNR-1, however, is expressed strongly in only some placodes and not in dorsolateral placodes, indicating that neurogenesis in the latter relies on other determination genes. X-Delta-1 is expressed not only in the neurogenic parts of the placodes but also in the primordia of the lateral lines. This suggests that Delta-Notch-mediated lateral inhibition may be involved not only in placodal neurogenesis, but also in the patterning of lateral line neuromasts.

Animals↗

Loss of ectodermal competence for lateral line placode formation in the direct developing frog Eleutherodactylus coqui.

In the direct-developing frog Eleutherodactylus coqui neuromasts and ganglia of the lateral line system never develop. We show here that this absence of the lateral line system, which is evolutionarily derived in anurans, is due to very early changes in development. Ectodermal thickenings, which are typical of lateral line placodes, and from which neuromasts and ganglion cells of the lateral line originate, never form in E. coqui, although other neurogenic placodes are present. Moreover, although NeuroD is expressed in the lateral line placodes of Xenopus laevis, corresponding expression sites are lacking in E. coqui. Heterospecific transplantation experiments show that axolotl ectoderm can be induced to form lateral line placodes after transplantation to E. coqui hosts but that E. coqui ectoderm does not form lateral line placodes on axolotl hosts. This suggests that the loss of the lateral line system in E. coqui is due to the specific loss of ectodermal competence to form lateral line placodes in response to inductive signals. Our results (1) indicate that the competence for lateral line placode formation is distinct and dissociable from the competence to form other neurogenic placodes and (2) support the idea that the lateral line system acts as a module in development and evolution.

Animals↗

Development of the retina is altered in the directly developing frog Eleutherodactylus coqui (Leptodactylidae).

The loss of a free-living larval stage during the evolution of directly developing frogs of the genus Eleutherodactylus resulted in dramatic alterations in ontogeny. Immunostaining for proliferating cell nuclear antigen reveals that in the directly developing frog Eleutherodactylus coqui pervasive cell proliferation occurs throughout the retina even after the plexiform layers have formed. In striking contrast to biphasically developing frogs (e.g. Discoglossus pictus or Xenopus laevis), in E. coqui proliferation becomes restricted to the ciliary margin only after the eye has reached the size typical of a postmetamorphic froglet and after its laminar structure has developed. As a consequence, the retina of E. coqui develops rapidly without recapitulating larva-typical stages. Our results suggest that dissociation of cell proliferation and differentiation can lead to the abbreviation of ontogenies during evolution.

Animals↗

Evolution of nerve development in frogs. I. The development of the peripheral nervous system in Discoglossus pictus (Discoglossidae).

The gross anatomical development of the peripheral nervous system (PNS) during embryogenesis and metamorphosis in the frog Discoglossus pictus is described based on whole-mount immunostaining for nerves and muscles. In the head, neurite outgrowth starts with the mandibular ramus of the trigeminal nerve at the tailbud stage. Cranial muscles are innervated as soon as they differentiate, beginning at mid-embryonic stages. During late embryonic stages, the course of the trigeminal and facial nerves becomes greatly distorted and changes again drastically during metamorphosis accompanying the reorganization of the jaw muscles. Two occipital somites and nerves develop transitorily but degenerate at late embryonic stages. The hypoglossal nerve develops by fusion of the first and second spinal nerves and receives a transitory contribution of the third and fourth spinal nerve at embryonic stages. In the trunk, several classes of Rohon-Beard neurites could be identified at embryonic stages, one of which forms intersegmental sensory nerves that prefigure the course of the sensory rami of spinal nerves at later stages. We give detailed schedules of PNS and cranial muscle development which, in comparison with data on other frog species described in a companion paper, will serve as a basis to evaluate heterochronic shift during evolution of PNS development in frogs.

Animals↗

Evolution of nerve development in frogs. II. Modified development of the peripheral nervous system in the direct-developing frog Eleutherodactylus coqui (Leptodactylidae).

We use whole-mount immunohistochemistry to describe the pattern of development of cranial nerves and muscles in the direct-developing leptodactylid frog Eleutherodactylus coqui. Comparison with nerve development in the biphasically developing frogs Physalaemus pustulosus (Leptodactylidae) and Discoglossus pictus (Discoglossidae; described in a companion paper) allows us to infer the ancestral leptodactylid ontogenetic pattern and the extent to which it has been modified during the evolution of direct development in Eleutherodactylus. While early embryonic development of cranial nerves and muscles is remarkably conserved in E. coqui, most transitory embryonic and larval characters (e.g., occipital and spinal myotomes together with their innervation, the distorted course of trigeminal and facial nerves, ventral branchial arch muscles, a subset of branchial-nerve rami and the lateral-line system) never develop. However, a few larva-typical characters are recapitulated, including Rohon-Beard cells and an anastomosis between the vagal and hypoglossal nerve. In addition to the abbreviation of ontogeny by loss of larva-specific traits, dramatic dissociations and heterochronic shifts of characters can be observed in E. coqui. The onset of development of limb and trunk innervation has been pre-displaced to early embryonic stage. Moreover, the reorientation of cranial muscles and nerves corresponding to late metamorphic events in biphasically developing anurans occurs relatively much earlier and is less pronounced in E. coqui resulting in an extreme condensation of ontogeny.

Animals↗

Distribution of cranial and rostral spinal nerves in tadpoles of the frog Discoglossus pictus (Discoglossidae).

We studied the peripheral nervous system of early tadpoles of the frog Discoglossus pictus using whole-mount immunohistochemistry. Double-labeling of muscles and nerves allowed us to determine the innervation of all cranial muscles supplied by the trigeminal, facial, glossopharyngeal, vagal, and hypoglossal nerves. The gross anatomical pattern of visceral, cutaneous, and lateral-line innervation was also assessed. Most muscles of the visceral arches are exclusively supplied by posttrematic rami of the corresponding branchiomeric nerves, the only exceptions being some ventral muscles (intermandibular, interhyoid, and subarcual rectus muscles). In the mandibular arch, the pattern of motor ramules of the trigeminal nerve prefigures in a condensed form the adult pattern, but the muscles of the hyoid arch are innervated by ramules of the facial nerve in a pattern that differs from that of postmetamorphic frogs. With respect to the nerves of the branchial arches, pretrematic visceral rami, typical of other gnathostomes, are absent in D. pictus. Instead, we find a separate series of posttrematic profundal visceral rami. Pharyngeal rami of all branchial nerves contribute to Jacobson's anastomosis. We provide a detailed description of the lateral-line innervation and describe a new ramus of the middle lateral-line nerve (ramus suprabranchialis). We confirm the presence of a first spinal nerve and its contribution to the hypoglossal nerve in D. pictus tadpoles.

Animals↗

Lipoprotein (a), low-density, intermediate-density lipoprotein, and blood pressure in a young male population.

Both hypercholesterolemia and hypertension are risk factors for atherosclerotic vascular disease, and elevated cholesterol levels occur more frequently than expected in patients with hypertension. Elevated levels of intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) were shown to be atherogenic, and LDL, comprising the major cholesterol-carrying fraction in human plasma, are structurally related to lipoprotein (a)[Lp(a)], a further risk factor for atherosclerosis. In the present study we investigated 200 male employees (mean age 26 +/- 7 years) to determine whether the relationship of IDL and Lp(a) to systemic blood pressure is similar to the reported correlations between total and LDL cholesterol and systemic blood pressure. To this end blood pressure was measured several times in each individual, and lipids, lipoprotein-cholesterol, apolipoprotein B (apo B), and Lp(a) were determined in fasting serum. IDL cholesterol and apo B, the main protein component of IDL and LDL correlated with blood pressure. However, levels of Lp(a) correlated neither with systolic or diastolic blood pressure nor with lipoprotein cholesterol, body weight, or age. Although IDL and Lp(a) are considered lipoprotein risk factors for atherosclerosis, levels of Lp(a), unlike IDL, are not related to blood pressure, body weight, or age. Our data suggest different metabolic and pathophysiological mechanisms of the risk factors, IDL, LDL, and Lp(a).

Adult↗

An analysis of rheumatology cases presenting to the emergency room of a teaching hospital.

We surveyed diagnoses on 5592 consecutive new cases presenting to a general hospital emergency room. The number of cases that could be judged "rheumatic" were analyzed further to determine the spectrum of rheumatologic problems that were seen in this facility. Four hundred eighty-three cases were studied. Precise diagnosis frequently could not be determined, but the largest group was soft tissue rheumatism. A wide variety of "rheumatologic" cases were seen initially in the emergency room. The clinical disposition and followup on these patients was also determined.

Emergency Medical Services↗

Projection-neurons that send axons through the lumbar spinal cord of the chick embryo are not obviously distributed in a segmentally repetitive pattern.

Earlier studies have shown that the formation of the segmentally repetitive pattern of spinal nerves in avian embryos depends upon the segmental arrangement of the somites and does not reflect an intrinsic pattern of the spinal cord. These studies could not, however, rule out the possibility that some elements of the central nervous system are intrinsically segmented. The question remained, for instance, whether projection-neurons are distributed in a segmentally repetitive pattern within the spinal cord. To address this question, horseradish peroxidase was injected into one or two segments of the lumbar spinal cord of chick embryos, thereby labeling projection-neurons that had ascending or descending axons passing through the injection site. In all stages examined, the number of labeled projection-neurons in the anterior and posterior halves of each segment did not differ significantly. In addition, segmentally repetitive peaks or troughs in the numbers of labeled projection-neurons were not detected in the center of each segment. Three subpopulations of projection-neurons, defined by their position along the dorsal-ventral axis of the spinal cord, were also not segmentally distributed by these criteria. While these results do not rule out the possibility that subpopulations of projection-neurons defined by dendritic morphology, functional class, or some other parameter are segmentally arranged or that there is a basic modular repetition of neural populations from segment to segment, they do show that projection-neurons as a class and subpopulations of these neurons defined by their dorsal-ventral position are not obviously distributed in a repetitive segmental pattern.

Animals↗