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PubMed1997

On the presence of dendrite bundles in the cerebral cortex of the Madagascan lesser hedgehog tenrec and the red-eared pond turtle.

In mammals with a well-differentiated neocortex apical dendrites of pyramidal cells form vertical bundles. Little is known about the presence of dendrite bundles in animals with a poorly differentiated cortex. In this paper the presence of dendrite bundles has been investigated in the lesser hedgehog tenrec, Echinops telfairi, a basal insectivore with a very low degree of neocorticalization. In a further step the arrangement of dendrites has been analyzed in the cerebral cortex of the red-eared pond turtle, Pseudemys scripta elegans. Among non-mammalian vertebrates, reptiles have a cerebral cortex that is relatively most comparable with the mammalian one, and the cerebral cortex of turtles shows more structural and functional similarities with the cortex in mammals than those of other reptiles. In the hedgehog tenrec, bundles of apical dendrites are found in all neo-cortical areas, the cingulate and retrosplenial cortices. The shape and arrangement of dendrite bundles are primarily determined by apical dendrites of lamina V pyramids. Apical dendrites originating in laminae III/IV or VI join these bundles, and do not give rise to separate sets of bundles in the supra- and infragranular layers as in other mammals. Center to center distances between bundles determined in the neocortical areas A(2-4) range from 7 to 76 microm, with an average of 32 microm. Area-specific differences are found concerning the length of bundles as well as the number, caliber, branching pattern and packing density of dendrites sharing an individual bundle. In the three-layered entorhinal cortex and the hippocampus dendrite bundles are not observed. In the turtle, no vertical bundles of dendrites are seen either in the medial, dorsomedial or medial part of the dorsal cortex. Only in the lateral part of the dorsal cortex are isolated bundles of apical dendrites originating from groups of perikarya situated below the main level of lamina II detected. Our findings suggest that the presence of dendrite bundles is closely related with the multilayered nature of the mammalian neocortex.

Animals↗
PubMed2004

Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation.

UNLABELLED: Mutations in the human sonic hedgehog gene (SHH) are the most frequent cause of autosomal dominant inherited holoprosencephaly (HPE), a complex brain malformation resulting from incomplete cleavage of the developing forebrain into two separate hemispheres and ventricles. Here we report the clinical and molecular findings in five unrelated patients with HPE and their relatives with an identified SHH mutation. Three new and one previously reported SHH mutations were identified, a fifth proband was found to carry a reciprocal subtelomeric rearrangement involving the SHH locus in 7q36. An extremely wide intrafamilial phenotypic variability was observed, ranging from the classical phenotype with alobar HPE accompanied by typical severe craniofacial abnormalities to very mild clinical signs of choanal stenosis or solitary median maxillary central incisor (SMMCI) only. Two families were initially ascertained because of microcephaly in combination with developmental delay and/or mental retardation and SMMCI, the latter being a frequent finding in patients with an identified SHH mutation. In other affected family members a delay in speech acquisition and learning disabilities were the leading clinical signs. CONCLUSION: mutational analysis of the sonic hedgehog gene should not only be considered in patients presenting with the classical holoprosencephaly phenotype but also in those with two or more clinical signs of the wide phenotypic spectrum of associated abnormalities, especially in combination with a positive family history.

Adult↗
PubMed1998

Analysis of the human Sonic Hedgehog coding and promoter regions in sacral agenesis, triphalangeal thumb, and mirror polydactyly.

The human Sonic Hedgehog gene (SHH) is one of the vertebrate homologs related to the Drosophila segment polarity gene hedgehog. The entire coding and promoter region of the SHH gene, including 2 kb 5' of the transcriptional start site has been screened for mutations in families with autosomal dominant sacral agenesis and autosomal dominant triphalangeal thumb, two conditions previously known to be linked to 7q36. We have also studied the SHH gene in five families with mirror polydactyly associated with tibial hemimelia and in 51 unrelated patients with neural tube defects. Except for two sequence variants in exon 3, no mutations were found in these disease categories. OFF

Abnormalities, Multiple↗
PubMed2000

Role of parathyroid hormone-related peptide and Indian hedgehog in skeletal development.

Parathyroid hormone-related peptide (PTHrP), which frequently causes the humoral hypercalcemia of malignancy syndrome, is an autocrine/paracrine regulator of chondrocyte proliferation and differentiation that acts through the PTH/PTHrP receptor (PTH1R). PTHrP is generated in response to Indian hedgehog (Ihh), which mediates its actions through the membrane receptor patched, but interacts also with hedgehog-interacting protein (Hip). Mice lacking PTHrP show accelerated chondrocyte differentiation, and thus premature ossification of those bones that are formed through an endochondral process, and similar but more-severe abnormalities are observed in PTH1R-ablated animals. The mirror image of these skeletal findings, i.e., a severe delay in chondrocyte differentiation and endochondral ossification, is observed in transgenic mice that overexpress PTHrP under the control of the alpha1(II) procollagen promoter. Severe abnormalities in chondrocyte proliferation and differentiation are also observed in two genetic disorders in humans that are most likely caused by mutations in the PTH1R. Heterozygous PTH1R mutations that lead to constitutively activity were identified in Jansen metaphyseal chondrodysplasia, and homozygous or compound heterozygous mutations that lead to less-active or completely inactive receptors were identified in patients with Blomstrand lethal chondrodysplasia. Based on the growth plate abnormalities observed in these human disorders and in mice with abnormal expression of either PTHrP or the PTH1R, it appears plausible that impaired expression of PTHrP and/or its receptor contributes to the growth abnormalities in children with end-stage renal disease. In fact, mild-to-moderate renal failure leads in animals to a reduction in PTH1R expression in growth plates and impaired growth, but it remains uncertain whether this contributes to altered chondrocyte growth and differentiation.

Animals↗
PubMed2004

Sonic hedgehog delivered by an adeno-associated virus protects dopaminergic neurones against 6-OHDA toxicity in the rat.

Direct intracerebral administration of sonic hedgehog (SHH) reduces 6-OHDA and MPTP toxicity to nigral dopaminergic cells in rats and primates. To determine whether transfection of the DNA sequence for SHH using viral vectors also protects against 6-OHDA toxicity, a type 2 adeno- associated virus (AAV) incorporating 600 base pairs of N-terminal SHH DNA was generated to induce SHH expression in rat striatum.AAV-SHH was injected into the striatum, 3 weeks prior to the initiation of an unilateral partial 6-OHDA nigro-striatal lesion. Animals receiving 4x10(7) viral particles of AAV-SHH showed a reduction in (+)-amphetamine induced ipsilateral turning over 4 weeks, when compared to animals receiving vehicle or a LacZ encoding vector. Following vehicle or AAV-LacZ administration, 6-OHDA caused a marked loss of striatal dopamine content and nigral tyrosine hydroxylase (TH) immunopositive cells. Following treatment with 4x10(7) viral particles of AAV-SHH the loss of striatal dopamine content was reduced and there was marked preservation of nigral dopaminergic cells. However, administration of 4x10(8) particles of AAV-SHH did not cause a significant change in (+)-amphetamine-induced rotation, striatal dopamine levels or the number of nigral TH immunoreactive cells following 6-OHDA lesioning compared to vehicle or AAV-LacZ treated animals. The results show that SHH delivered via a viral vector can protect dopaminergic neurons against 6-OHDA toxicity and suggest that this could be developed into a novel treatment for PD. However, the effects maybe dose limited due to uncoupling of hedgehog receptor signalling at higher levels of SHH expression.

Adenoviridae↗
PubMed2006

Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro.

BACKGROUND: Sonic hedgehog (Shh) protein is known to be an important signaling protein in early embryonic development. Also, Shh is involved in the induction of early cartilaginous differentiation of mesenchymal cells in the limb and in the spine. METHODS: The impact of Shh on adult stem cells, human bone marrow-derived mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factor-beta 1 (TGF-beta(1)) as a positive control in vitro for 3 weeks. The effects on cartilaginous differentiation and proliferation were assayed. RESULTS: MSCs when treated with either Shh or TGF-beta(1) showed expression of cartilage markers aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh-treated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems. CONCLUSIONS: These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.

Adult↗
PubMedDate not supplied

Methoprene photolytic compounds disrupt zebrafish development, producing phenocopies of mutants in the sonic hedgehog signaling pathway.

Environmental chemicals have been proposed to impact endocrine or retinoid pathways, causing developmental abnormalities in humans and other vertebrates. Presented evidence shows that exposure of zebrafish embryos to sunlight-induced photolytic products of the pesticide methoprene results in developmental defects in the head, heart, pectoral fins, and somites, and in spinal motor and optic nerve axons. Exposed embryos are phenocopies of zebrafish you-type mutants and, as in the mutant sonic-you, show underexpression of the signaling protein sonic hedgehog. Reduced expression of sonic hedgehog is also displayed in embryos treated with the retinoic acid synthesis inhibitor citral. This study identifies citral-related compounds as embryonic signaling disruptors of potential environmental concern.

Animals↗
PubMed1986

Histochemical enzyme profile of the masseter, temporal and lateral pterygoid muscles of the European hedgehog (Erinaceus europeaus).

In man, there are large differences in histochemical fibre-type composition, distribution and size between jaw and trunk muscles, probably related to the special functions of the human stomatognathic system. In the hedgehog, the influence of alkaline and acid pre-incubations on the reaction for myofibrillar ATPase was different from that in man, suggesting a different myosin structure; the fibre composition was different also. The masseter, the superficial portion of the temporal and the lateral pterygoid muscles all showed a homogeneous fibre type profile with almost 100 per cent alkali-stable fibres. In two animals, the deep temporal muscles showed an apparent heterogeneous fibre pattern with 81 per cent alkali-stable fibres, 4 per cent alkali-labile fibres and 15 per cent ATPase-intermediate fibres; in one animal 87 per cent alkali-stable fibres and 13 per cent ATPase-intermediate fibres. There was no difference in cross-sectional area between the three fibre types within each muscle, but the fibres of the lateral pterygoid were smaller than the alkali-stable and the alkali-labile fibres of the masseter and temporal muscles. The limb and trunk muscles showed reactions for myofibrillar ATPase similar to the jaw muscles, but had a heterogeneous fibre-type profile. There was no significant difference in cross-sectional fibre area between the jaw and the limb muscles. Thus the jaw and limb muscles of the hedgehog have similar fibre types and about equal fibre size.

Adenosine Triphosphatases↗
PubMed1989

Seasonal variations of plasma lipids and lipoproteins in the hedgehog, an animal model for lipoprotein (a) metabolism: relation to plasma thyroxine and testosterone levels.

We describe a study of the seasonal variations of hedgehog plasma lipids and lipoproteins and their correlation with changes in the activities of the thyroid and testis. In ten male hedgehogs, plasma concentrations of lipids, thyroxine and testosterone were assayed each month for 1 year beginning in September, while plasma lipoproteins from five of these animals were analyzed at the same dates using density gradient ultracentrifugation. All classes of plasma lipids (cholesterol, total glycerol and phospholipids) exhibited statistically significant seasonal variations in their respective concentrations, with simultaneous maxima (cholesterol: 207 +/- 39 mg/100 ml; total glycerol: 50 +/- 9 mg/100 ml; phospholipids: 266 +/- 25 mg/100 ml) during late fall-early winter, i.e., during the period of the year when plasma levels of both thyroxine and testosterone were minimal. Plasma lipids subsequently decreased to minimal levels either in early summer (cholesterol: 129 +/- 18 mg/100 ml; phospholipids: 178 +/- 20 mg/100 ml) or in late winter (total glycerol: 22 +/- 9 mg/100 ml). Very low density lipoproteins (d less than 1.015 g/ml) were found at low levels (less than 15 mg/100 ml) during the cold months, and then became detectable as trace components only. The total concentration of the mixed lipoprotein population (i.e., low density lipoproteins, Lp(a), and high density lipoprotein (HDL)-like particles) in the d 1.015-1.065 g/ml interval decreased by almost 50% from January to February (from 164.3 to 89.2 mg/100 ml), i.e., following a 10-fold increase in the level of plasma testosterone, and immediately before the rapid doubling in plasma thyroxine concentration. The staining intensity of the electrophoretic band with migration characteristics corresponding to those of Lp(a) decreased considerably during winter. At the same period of the year, lower density (1.032-1.055 g/ml) HDL-like particles disappeared. The concentration of lipoproteins with d 1.065-1.162 g/ml, which included Lp(a) particles in addition to typical HDL, equally underwent seasonal variations. These variations consisted of two successive maxima in late fall (426.4 mg/100 ml) and late winter (458.3 mg/100 ml) with two subsequent decreases leading to minima in February (327.8 mg/100 ml) and August (257.1 mg/100 ml). Finally, very high density lipoproteins (d 1.162-1.259 g/ml) were heterogeneous, containing both cholesterol-rich (d 1.162-1.227 g/ml) and phospholipid-rich (d 1.194-1.259 g/ml) subpopulations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1980

Photically evoked potentials and afterpotentials recorded from the visual cortex of the unanesthetized hedgehog.

Evoked potentials to visual stimuli (VEP) were recorded from the visual cortex of the unanesthetized hedgehog (Erinaceus europaeus), a primitive placental mammal with relatively little differentiation of cortex and thalamus. The VEPs consisted of several distinct positive and negative voltage deflections. Reproducibility of the response was high, as indicated from the small intrasession and intersession response variability. Rhythmic afterpotentials (AP), previously reported for higher mammals, were readily elicited. They had a lower frequency (3/sec) than APs observed in other mammals. The use of the hedgehog in electrophysiological and psychophysiological research is suggested because data obtained from this primitive placental mammal may shed light on CNS functions of higher mammals, as well as mammalian forms 'lower' on the evolutionary scale.

Animals↗
PubMed1985

Entorhinal and prepiriform cortices of the European hedgehog. A histochemical and densitometric study based on a comparison between Timm's sulphide silver method and the selenium method.

The Timm and selenium staining techniques, based on silver amplification of endogenous zinc, produce an electron-dense precipitate in boutons. The staining characteristics of the two methods were compared by examining two allocortical regions, prepiriform cortex and entorhinal cortex, in the brain of the European hedgehog. In the 3 layers of prepiriform cortex and the 6 layers of entorhinal cortex the methods revealed sublayers, which allows a precise delimitation of areas 28M, 28L, a short transition zone, and the prepiriform cortex. The lamination of the entorhinal cortex of the hedgehog is similar to that found in the rat, but appears less distinct. This may point to a lower degree of afferent organization. For light microscopical investigations, the selenium technique appears superior to Timm's method because it produces a more distinct zonation pattern.

Animals↗
PubMed1991

Demonstration of a phospholipase A2 inhibitor in human plasma and in plasma from the European hedgehog (Erinaceus europaeus).

1. Endogenous phospholipase A2 (PLA2) inhibitors in human plasma and in plasma from the hedgehog (Erinaceus europaeus) were demonstrated. 2. The PLA2 activity increased 45-fold in human plasma when a PLA2 binding factor was removed. Furthermore, two peaks of PLA2 inhibitory activity were found after DEAE-chromatography. 3. High levels of PLA2 inhibitory activity was found in plasma from the European hedgehog, E. europaeus. 4. The molecular weight was estimated to 140,000. 5. On DEAE-chromatography two peaks were found which were chromatographically similar to the PLA2 inhibitors in human plasma.

Adult↗
PubMed1995

Long-range sclerotome induction by sonic hedgehog: direct role of the amino-terminal cleavage product and modulation by the cyclic AMP signaling pathway.

A long-range signal encoded by the Sonic hedgehog (Shh) gene has been implicated as the ventral patterning influence from the notochord that induces sclerotome and represses dermomyotome in somite differentiation. Long-range effects of hedgehog (hh) signaling have been suggested to result either from local induction of a secondary diffusible signal or from the direct action of the highly diffusible carboxy-terminal product of HH autoproteolytic cleavage. Here we provide evidence that the long-range somite patterning effects of SHH are instead mediated by a direct action of the amino-terminal cleavage product. We also show that pharmacological manipulations to increase the activity of cyclic AMP-dependent protein kinase A can selectively antagonize the effects of the amino-terminal cleavage product. Our results support the operation of a single evolutionarily conserved signaling pathway for both local and direct long-range inductive actions of HH family members.

Animals↗
PubMed1995

Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube.

The vertebrate hedgehog-related gene Sonic hedgehog (Shh) is expressed in ventral domains along the entire rostrocaudal length of the neural tube, including the forebrain. We show here that SHH induces the differentiation of ventral neuronal cell types in explants derived from prospective forebrain regions of the neural plate. Neurons induced in explants derived from both diencephalic and telencephalic levels of the neural plate express the LIM homeodomain protein Isl-1, and these neurons possess distinct identities that match those of the ventral neurons generated in these two subdivisions of the forebrain in vivo. A single inducing molecule, SHH, therefore appears to mediate the induction of distinct ventral neuronal cell types along the entire rostrocaudal extent of the embryonic central nervous system.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed1993

The primary structure of pancreatic polypeptide from a primitive insectivorous mammal, the European hedgehog (Erinaceous europaeus).

Pancreatic polypeptide (PP) has been isolated from extracts of the pancreas of the European hedgehog (Erinaceous europaeus) which is a representative of the order Insectivora, deemed to be the most primitive group of placental mammals. Pancreatic tissues were extracted in acidified ethanol and the peptide was purified chromatographically using a PP C-terminal hexapeptide amide specific radioimmunoassay to monitor purification. Two major PP-immunoreactive peptides were baseline-resolved following the final analytical reverse phase HPLC fractionation. Each was separately subjected to plasma desorption mass spectroscopy (PDMS) and gas-phase sequencing. The molecular masses of each peptide were similar: (I) 4237.6 +/- 4 Da and (II) 4238.2 +/- 4 Da. The full primary structures of each peptide were deduced and these were identical: VPLEPVYPGDNATPEQMAHYAAELRRYINMLTRPRY. The peptides were deemed to be amidated due to their full molar cross-reactivity with the amide-requiring PP antiserum employed in radioimmunoassay. The molecular mass (4233.8 Da) calculated from the sequence was in close agreement with PDMS estimates and the reason for the different retention times of each peptide is unknown at present. Hedgehog PP exhibits only 2 unique amino acid substitutions, at positions 1 (Val) and 19 (His), when compared with other mammalian analogues.

Amino Acid Sequence↗
PubMed1983

Hibernation-hypothermia and metabolism in hedgehogs. Changes in water and electrolytes.

1. Hedgehogs seem not to suffer water loss during hibernation or hypothermia probably through water shifts from the interstitium to the cells and/or protein catabolism in tissues. 2. Higher potassium concentrations were retained in hedgehog's tissues, sodium and chloride ions rose in plasma, but ionic gradients were slightly affected. Probable reasons for increased calcium, magnesium and inorganic phosphorus were discussed. 3. Changes recorded during late fall indicated the predisposition of animals to hibernate, while changes during spontaneous and full arousals showed a reversed phenomenon in the hibernation cycle. 4. Artificially hypothermic animals in summer showed results similar to those of naturally hypothermic in winter, although lower in magnitude, suggesting a specific role of temperature in regulating the hibernation cycle.

Animals↗
PubMed1983

Hibernation-hypothermia and metabolism in hedgehogs. Changes in some organic components.

1. Biochemical levels of certain carbohydrates, lipids and proteins were determined in plasma, liver and brain of the oriental hedgehog and compared in active, hypothermic and awake animals. 2. Lipid reserves exhibited significant increase in autumn before the onset of hibernation. This was bound up with the predisposition of the animal to hibernate. 3. During hypothermia, glucose levels, lipid reserves and tissue protein content significantly declined, in contrast to tissue glycogen which remarkably increased. 4. This indicated that glycogenolysis was impaired while gluconeogenesis from lipids and proteins presented the primary source of energy necessary for tissue requirements. 5. During arousal, the marked elevation in plasma glucose concomitant with the drop in tissue glycogen, lipids and proteins indicated that glycogenolysis as well as gluconeogenesis participated in glucose production necessary for the thermogenesis required during wakefulness. 6. Our data suggested that the accumulation of brain glycogen during winter may directly initiate arousal. 7. The nature of the biochemical changes that occurred throughout the hibernation cycle implies that metabolism in hedgehogs is influenced by dynamically balanced control mechanisms operating within a wide range of temperatures.

Animals↗
PubMed1996

Water turnover evaluated by the tritiated water method and by the nutritional method in European hedgehog (Erinaceus europaeus L.).

The total body water (TBW), the fractional water turnover rate (WTR), and the water flux rates (WFR) were studied for the first time by the tritiated-water method in 10 hedgehogs under laboratory conditions during the year. To validate this method, we compared the result to the nutritional method. The TBW varied inversely with body mass (BM) during both the active and the hibernation periods. The WTR varied from 16% to 21% during the hibernation period and after the reproduction. The higher values (from 22% to 26%) were recorded during the reproduction period and during the preparation for hibernation. The same variations in WFR were recorded during the active and hibernation period. The net gain or loss of water followed the gain and loss of BM. The tritiated water (THO) method has been validated by the fact that the same variations in WFR during each month have been measured by the THO method and the nutritional method. Moreover, the THO method can be used to estimate the changes in energy metabolism of hedgehogs in relation with the seasons.

Analysis of Variance↗