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PubMed2005

Analysis of the regulation of lin-41 during chick and mouse limb development.

We have cloned the chicken and mouse orthologues of the Caenorhabditis elegans heterochronic gene lin-41. During limb development, lin-41 is expressed in three phases over developmental time and most notably is associated with the developing autopod. Using chicken and mouse mutants and bead implantations, we report that lin-41 is genetically and biochemically downstream of both the Shh and Fgf signaling pathways. In C. elegans, it is proposed that lin-41 activity is temporally regulated by miRNAs (let-7 and lin-4) that bind to complementary sites in the lin-41 3'-untranslated region (UTR). Taking a bioinformatics approach, we also report the presence of potential miRNA binding sites in the 3'-UTR of chicken lin-41, including sites for the chicken orthologues of both C. elegans let-7 and lin-4. Finally, we show that these miRNAs and others are expressed in the chick limb consistent with the hypothesis that they regulate chicken Lin-41 activity in vivo.

Amino Acid Sequence↗
PubMed2003

Genetic isolation between two sympatric host-plant races of the European corn borer, Ostrinia nubilalis Hübner. I. Sex pheromone, moth emergence timing, and parasitism.

Adaptation to different environments may be a powerful source of genetic differentiation between populations. The biological traits selected in each environment can pleiotropically induce assortative mating between individuals of these genetically differentiated populations. This situation may facilitate sympatric speciation. Successful host shifts in phytophagous insects provide some of the best evidence for the ecological speciation that occurs, or has occurred, in sympatry. The European corn borer, Ostrinia nubilalis (Lepidoptera: Crambidae), colonized maize after its introduction into Europe by humans about 500 years ago. In northern France, two sympatric host races feed on maize (Zea mays) and mugwort (Artemisia vulgaris), respectively. We investigated the factors involved in the genetic isolation of these two races at a field site near Paris, France. We identified two biological differences that might make a significant contribution to the genetic divergence between sympatric populations feeding on the two host plants. First, assortative mating may be due to differences in the moth emergence pattern between the two races: mugwort-race moths emerged on average 10 days earlier than maize-race moths. In addition, the males emerged earlier than females in both races. Hence, the likelihood of mating between maize-race males and mugwort-race females was higher than that of mating between mugwort-race males and maize-race females. Second, the females feeding on mugwort and maize produced sex pheromones with different E/Z isomeric ratios of delta-11-tetradecenyl acetate. This difference in mate recognition systems reinforces the potential for assortative mating in the two races. During the experiment, overwintering mortality was much lower on maize than on mugwort. This difference was due to a braconid parasitoid wasp, Macrocentrus cingulum, that killed more than 50% of the larvae overwintering on mugwort but did not infest larvae diapausing on maize. Hence, by colonizing maize, European corn borer populations probably escaped from numerous predators, competitors, and parasitoids, such as M. cingulum. This decrease in host-associated selection may have favored the colonization of this new host. Finally, throughout this experiment we observed selection at two allozyme loci (or at linked loci): Tpi and Mpi. The Tpi locus is tightly linked with the genes involved in the response of the male to the sex pheromone and in developmental timing. The location of these traits on the Z chromosome may play a role in shortening the time required for the evolution of premating barriers.

Alleles↗
PubMed2005

Identification and partial characterization of the enzyme of omega: one of five putative DPP IV genes in Drosophila melanogaster.

The omega (ome) gene product is a modifier of larval cuticle protein 5 and its alleles (and duplicates) in the third instar of Drosophila melanogaster. Using deletion mapping the locus mapped to 70F-71A on the left arm of chromosome 3. A homozygote null mutant (ome 1) shows a pleiotropic phenotype that affected the size, developmental time of the flies, and the fertility (or perhaps the behavior) of homozygous mutant males. The omega gene was verified as producing a dipeptidyl peptidase IV (DPPIV) by genetic analysis, substrate specificity and pH optimum. The identity of the gene was confirmed as CG32145 (cytology 70F4) in the Celera Database (Berkeley Drosophila Genome Project), which is consistent with its deletion map position. The genomic structure of the gene is described and the decrease in DPPIV activity in the mutant ome1 is shown to be due to the gene CG32145 (omega). The D. melanogaster omega DPPIV enzyme was partially purified and characterized. The exons of the ome1 mutant were sequenced and a base substitution mutation in exon 4 was identified that would yield a truncated protein caused by a stop codon. A preliminary study of the compartmentalization of the omega DPPIV enzyme in several organs is also reported.

Amino Acid Sequence↗
PubMed2004

Developmental gene amplification and origin regulation.

Developmentally regulated gene amplification serves to increase the number of templates for transcription, yielding greatly increased protein and/or RNA product for gene(s) at the amplified loci. It is observed with genes that are very actively transcribed and during narrow windows of developmental time where copious amounts of those particular gene products are required. Amplification results from repeated firing of origins at a few genomic loci, while the rest of the genome either does not replicate, or replicates to a lesser extent. As such, amplification is a striking exception to the once-and-only-once rule of DNA replication and may be informative as to that mechanism. Drosophila amplifies eggshell (chorion) genes in the follicle cells of the ovary to allow for rapid eggshell synthesis. Sciara amplifies multiple genes in larval salivary gland cells that encode proteins secreted in the saliva for the pupal case. Finally, Tetrahymena amplifies its rRNA genes several thousand-fold in the creation of the transcriptionally active macronucleus. Due to the ease of molecular and genetic analysis with these systems, the study of origin regulation has advanced rapidly. Comparisons reveal an evolutionarily conserved trans-regulatory apparatus and a similar organization of sequence-specific cis-regulatory replicator and origin elements. The studies indicate a regulatory role for chromatin structure and transcriptionally active genes near the origins.

Animals↗
PubMed2001

Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function.

The secreted protein encoded by the Sonic hedgehog (Shh) gene is localized to the posterior margin of vertebrate limb buds and is thought to be a key signal in establishing anterior-posterior limb polarity. In the Shh(-/-) mutant mouse, the development of many embryonic structures, including the limb, is severely compromised. In this study, we report the analysis of Shh(-/-) mutant limbs in detail. Each mutant embryo has four limbs with recognizable humerus/femur bones that have anterior-posterior polarity. Distal to the elbow/knee joints, skeletal elements representing the zeugopod form but lack identifiable anterior-posterior polarity. Therefore, Shh specifically becomes necessary for normal limb development at or just distal to the stylopod/zeugopod junction (elbow/knee joints) during mouse limb development. The forelimb autopod is represented by a single distal cartilage element, while the hindlimb autopod is invariably composed of a single digit with well-formed interphalangeal joints and a dorsal nail bed at the terminal phalanx. Analysis of GDF5 and Hoxd11-13 expression in the hindlimb autopod suggests that the forming digit has a digit-one identity. This finding is corroborated by the formation of only two phalangeal elements which are unique to digit one on the foot. The apical ectodermal ridge (AER) is induced in the Shh(-/-) mutant buds with relatively normal morphology. We report that the architecture of the Shh(-/-) AER is gradually disrupted over developmental time in parallel with a reduction of Fgf8 expression in the ridge. Concomitantly, abnormal cell death in the Shh(-/-) limb bud occurs in the anterior mesenchyme of both fore- and hindlimb. It is notable that the AER changes and mesodermal cell death occur earlier in the Shh(-/-) forelimb than the hindlimb bud. This provides an explanation for the hindlimb-specific competence to form autopodial structures in the mutant. Finally, unlike the wild-type mouse limb bud, the Shh(-/-) mutant posterior limb bud mesoderm does not cause digit duplications when grafted to the anterior border of chick limb buds, and therefore lacks polarizing activity. We propose that a prepattern exists in the limb field for the three axes of the emerging limb bud as well as specific limb skeletal elements. According to this model, the limb bud signaling centers, including the zone of polarizing activity (ZPA) acting through Shh, are required to elaborate upon the axial information provided by the native limb field prepattern.

Animals↗
PubMed2026

Post-transcriptional regulation of Profilin-2 by microRNAs and RNA-binding proteins forms a critical regulatory node for early embryonic cell fate decisions.

Post-transcriptional control by RNA binding proteins (RBPs) and microRNAs play central roles in mRNA stability and translation, yet how RBPs and microRNAs coordinate in developmental time to regulate cell fate remains poorly understood. Here, we demonstrate that post-transcriptional regulation of the Profilin 2 (Pfn2) transcript is essential for differentiation of embryonic stem cells (ESCs) into the primary germ layer lineages. The Pfn2 3'untranslated region has both an Iron Regulatory Protein binding site (IRE) and a nearby binding site for ESC enriched microRNAs. Deletion of this microRNA site leads to increased PFN2 and reduced FGF signaling during pluripotency transition prior to germ layer formation. In contrast, deletion of the IRE leads to decreased PFN2, a Wnt signaling defect, reduced nuclear beta-catenin, and a subsequent block in mesendodermal lineages during early germ layer formation. We further find that loss of the IRE site results in a cell autonomous defect in Wnt signaling and mesendodermal differentiation. The IRE site acts to stabilize beta-catenin, as disruption of the site leads to reduced nuclear beta-catenin levels. Together, these findings reveal the Pfn2 microRNA-IRE regulatory axis as a critical post-transcriptional regulatory node governing the switch from pluripotency to somatic differentiation.

MicroRNAs↗
PubMed1999

Resetting and postnatal maturation of oxygen chemosensitivity in rat carotid chemoreceptor cells.

1. Carotid chemoreceptor sensitivity is minimal immediately after birth and increases with postnatal age. In the present study we have investigated the peri- and postnatal developmental time course of [Ca2+]i responses to hypoxia in clusters of type I cells isolated from near-term fetal rats and rats that were 1, 3, 7, 11, 14 and 21 days old, using the Ca2+-sensitive fluoroprobe fura-2. 2. In type I cells from all age groups a graded increase in [Ca2+]i occurred in response to lowering the PO2 from 150 mmHg to 70, 35, 14, 7, 2 and 0 mmHg. The graded [Ca2+]i response to hypoxia was hyperbolic at all ages. 3. Type I cells from rats near-term fetal to 1 day old exhibited small [Ca2+]i responses, mainly to the most severe levels of hypoxia. After day 1, an increase in the [Ca2+]i responses to submaximal hypoxia stimulation resulted in a rightward shift in the O2 response curve. Using the Delta[Ca2+]i between 35 and 2 mmHg PO2 as an index of O2 sensitivity, type I cell O2 sensitivity increased approximately 4- to 5-fold between near-term fetal to 1 day old and 11 to 14 days of age. 4. Exposure to elevated extracellular potassium (10, 20 and 40 mM K+) caused a dose-dependent [Ca2+]i rise in type I cells from all age groups. There were no age-related changes in [Ca2+]i responses to any level of K+ between near-term fetal and 21 days. 5. We conclude that the maximal type I cell [Ca2+]i response to anoxia, as well as the sensitivity to submaximal hypoxic stimulation, of rats aged from near-term fetal to 21 days depends on the level of postnatal maturity. The lack of an age-related increase in the [Ca2+]i response to elevated K+ during the timeframe of maximal development of O2 sensitivity suggests that resetting involves maturation of O2 sensing, rather than non-specific developmental changes in the [Ca2+]i rise resulting from depolarization.

Aging↗
PubMedDate not supplied

Expression of connexins during development and following manipulation of afferent input in the rat locus coeruleus.

Synchronous activity of locus coeruleus (LC) neurons during early postnatal development is regulated, in part, by electrotonic coupling. Connexin (Cx) proteins that make up gap junction channels are localized to both neurons and glia in the LC during this period. In adult rats, however, synchrony exists only under certain experimental conditions. The expression of Cx proteins was examined using western blot analysis at several developmental time points. Immunoblot analysis revealed little to no expression of Cx26 while Cx32, Cx43 and Cx36 were present at all time points examined. A progressive increase in Cx43 was identified from the first postnatal week through adulthood. Immunocytochemical detection of Cx36 and Cx43 in adult LC showed that Cx36 was associated with neuronal processes while Cx43 was localized to glia. In adult LC, in vitro intracellular recordings combined with neurobiotin injections confirmed the presence of gap junctional communication albeit to a lesser extent than in early postnatal periods. The degree to which synaptic inputs to LC neurons impact on Cx protein expression was also evaluated. Samples of the LC from rats that received an electrolytic lesion of the amygdala were processed for western blot analysis of Cx36 and Cx43. The predominantly neuronal Cx36 exhibited an increase in expression while the glial Cx43 was unchanged. The present results indicate that, despite subtype-specific changes during development, several Cx proteins are expressed in the adult LC. In addition, manipulating afferent input to the LC, in adult rats, results in increases in neuronal Cx protein levels but not in glial Cx levels suggesting that altering synaptic inputs to the LC may alter synchronous activity in noradrenergic neurons.

Afferent Pathways↗
PubMed1995

Effect of temperature and humidity on longevity of unfed adults and on oviposition of engorged females of Dermacentor reticulatus (Ixodidae).

The effect of ambient temperature and relative humidity on longevity of unfed adult ticks and on oviposition of engorged female ticks of Dermacentor reticulatus was examined. The 50% mortality time of unfed adult ticks, incubated at 5 degrees C, 10 degrees C, 20 degrees C and 27 degrees C and humidities of 15%, 50% and 100%, increased irrespective of their sex with rising relative humidity and decreasing temperature. It was longest at 5 degrees C and 100% r.h. being 617.8 days and shortest at 27 degrees C and 15% r.h. amounting only to 33.6 days. All unfed ticks survived an incubation of 150 days at -10 degrees C and 15%, 50% and 100% r.h. as well as an exposure of 180 days at 0 degrees C and 100% r.h. At 0 degrees C the percent survival was 75% for the males and 40% for the females at 50% r.h. but 100% for males and 95% for the females at 15% r.h. after exposure of 180 days. Oviposition of engorged females occurred at a temperature range of 10-27 degrees C, at 10 degrees C merely at 50% and 100% r.h. The percentage of ovipositioning females amounted to at least 80% apart from 10 degrees C and 50% r.h. being only 10%. The egg index and the egg conversion index as well as the larvae index and the larvae conversion index generally increased with rising temperature and relative humidity. The indices were lowest at 10 degrees C and 50% r.h. and were highest at 20 degrees C and 27 degrees C at 100% r.h. The reproduction capability of engorged female ticks, held at -10 degrees C, 0 degrees C and 5 degrees C and 15%, 50% and 100% r.h. and transferred to 20 degrees C and 95% r.h., persisted for 10 weeks at -10 degrees C and for 2 weeks at 0 degrees C at the most, but for at least 20 weeks at 5 degrees C. There were no significant differences of the preoviposition periods, egg indices and larvae indices as well as of the minimum embryonic developmental times and hatching rates with regard to the preceding incubation conditions and the length of the ticks' exposure.

Animals↗
PubMed2000

Functional properties, developmental regulation, and chromosomal localization of murine connexin36, a gap-junctional protein expressed preferentially in retina and brain.

Retinal neurons of virtually every type are coupled by gap-junctional channels whose pharmacological and gating properties have been studied extensively. We have begun to identify the molecular composition and functional properties of the connexins that form these 'electrical synapses,' and have cloned several that constitute a new subclass (gamma) of the connexin family expressed predominantly in retina and brain. In this paper, we present a series of experiments characterizing connexin36 (Cx36), a member of the gamma subclass that was cloned from a mouse retinal cDNA library. Cx36 has been localized to mouse chromosome 2, in a region syntenic to human chromosome 5, and immunocytochemistry showed strong labeling in the ganglion cell and inner nuclear layers of the mouse retina. Comparison of the developmental time course of Cx36 expression in mouse retina with the genesis of the various classes of retinal cells suggests that the expression of Cx36 occurs primarily after cellular differentiation is complete. Because photic stimulation can affect the gap-junctional coupling between retinal neurons, we determined whether lighting conditions might influence the steady state levels of Cx36 transcript in the mouse retina. Steady-state levels of Cx36 transcript were significantly higher in animals reared under typical cyclic-light conditions; exposure either to constant darkness or to continuous illumination reduced the steady-state level of mRNA approximately 40%. Injection of Cx36 cRNA into pairs of Xenopus oocytes induced intercellular conductances that were relatively insensitive to transjunctional voltage, a property shared with other members of the gamma subclass of connexins. Like skate Cx35, mouse Cx36 was unable to form heterotypic gap-junctional channels when paired with two other rodent connexins. In addition, mouse Cx36 failed to form voltage-activated hemichannels, whereas both skate and perch Cx35 displayed quinine-sensitive hemichannel activity. The conservation of intercellular channel gating contrasts with the failure of Cx36 to make hemichannels, suggesting that the voltage-gating mechanisms of hemichannels may be distinct from those of intact intercellular channels.

Animals↗
PubMed2004

Microarray analyses of gene expression during adventitious root development in Pinus contorta.

In order to investigate the gene expression pattern during adventitious root development, RNA of Pinus contorta hypocotyls, pulse-treated with the auxin indole-3-butyric acid and harvested at distinct developmental time points of root development, was hybridized to microarrays containing 2,178 cDNAs from Pinus taeda. Over the period of observation of root development, the transcript levels of 220 genes changed significantly. During the root initiation phase, genes involved in cell replication and cell wall weakening and a transcript encoding a PINHEAD/ZWILLE-like protein were up-regulated, while genes related to auxin transport, photosynthesis, and cell wall synthesis were down-regulated. In addition, there were changes in transcript abundance of genes related to water stress. During the root meristem formation phase the transcript abundances of genes involved in auxin transport, auxin responsive transcription, and cell wall synthesis, and of a gene encoding a B-box zinc finger-like protein, increased, while those encoding proteins involved in cell wall weakening decreased. Changes of transcript abundance of genes related to water stress during the root meristem formation and root formation phase indicate that the plant roots had become functional in water transport. Simultaneously, genes involved in auxin transport were up-regulated, while genes related to cell wall modification were down-regulated. Finally, during the root elongation phase down-regulation of transcripts encoding proteins involved in cell replication and stress occurred. Based on the observed changes in transcript abundances, we suggest hypotheses about the relative importance of various physiological processes during the auxin-induced development of roots in P. contorta.

Cell Division↗
PubMed2004

Regulatory role of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation in the immature mouse.

AIM: The aim of this study was to determine the action of bone morphogenetic proteins (BMPs) on testicular cell proliferation during early postnatal life, a definite developmental time at which crucial changes in germ cell and Sertoli cell maturation occur. METHODS: We investigated the effect of BMP2 and BMP7, two factors which belong to the relatively distant decapentaplegic (DPP) and 60 A classes of the large BMP family, upon spermatogonial and Sertoli cell proliferation, and we examined the expression of activin/BMP type II and type I receptors. We used in vitro cultured testis fragments from 7-day-old mice, highly purified populations of somatic and germ cells and total testes from mice of different ages. Cell proliferation was assessed by BrdU labelling and [3H]-thymidine incorporation. Ribonuclease protection assays and Northern blotting were performed to analyse receptor expression. RESULTS AND CONCLUSIONS: We have demonstrated a stimulatory action of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation respectively. ActRIIB is the type II receptor expressed most in spermatogonia, whereas Sertoli cells specifically expressed BMPRIIB, in addition to ActRIIB. By contrast, the presence of ActRIIA was undetectable in either germ or somatic cells. The type I receptors ActRIA, ActRIB and BMPRIA were all found in both cell types, indicating that the observed effect of BMP2 and BMP7 on testicular cell proliferation may be mediated by a number of combinatorial interactions in the receptor complexes. These findings suggest that BMPs are involved in physiological paracrine signalling during the first wave of spermatogenesis.

Activin Receptors↗
PubMedDate not supplied

Pedomorphosis revisited: thyroid hormone receptors are functional in Necturus maculosus.

Heterochrony, a difference in developmental timing, is a central concept in modern evolutionary biology. An example is pedomorphosis, retention of juvenile characteristics in sexually mature adults, a phenomenon largely represented in salamanders. The mudpuppy (Necturus maculosus) is an obligate pedomorphic amphibian, never undergoing metamorphosis. Thyroid hormone induces tissue transformation in metamorphosing species and this action is mediated by nuclear thyroid hormone (TH) receptors (TRs). The absence of metamorphosis in Necturus has been attributed to a resistance to TH action as treatment with exogenous TH fails to induce transformation. The failure to metamorphose could be due to the lack of TR expression in target tissues, or to a loss of TR function. Toward understanding the molecular basis for the failure of Necturus tissues to respond to TH, and the ultimate cause for the expression of the obligate pedomorphic life history, we characterized the structure, function, and expression of TR genes in Necturus. Strikingly, we found that Necturus TRalpha and TRbeta genes encode fully functional TR proteins. These TRs bind both DNA and TH and can transactivate target genes in response to TH. Both TRalpha and TRbeta are expressed in various tissues. TH treatment in vivo induced expression in the gill of some but not all genes known to be activated by TH in anuran larvae, caused whole organism metabolic effects, but induced no external morphological changes in adults or larvae. Thus, Necturus possesses fully functional TRs and its tissues are not generally resistant to the actions of TH. Rather, the absence of metamorphosis may be due to the loss of TH-dependent control of key genes required for tissue transformation.

Animals↗
PubMed2005

Abnormal mesenchymal differentiation in the superior semicircular canal of brn4/pou3f4 knockout mice.

OBJECTIVE: To examine the developmental time course of the mutant phenotype and cellular mechanisms that result in malformations of the superior semicircular canal (SSCC) in Brn4 knockout mice. Mutations in the Brn4/Pou3f4 gene result in characteristic inner ear abnormalities in mutant mouse pedigrees, and the findings in these mice are similar to those in human X-linked deafness type III. DESIGN: Mutant and control mice were killed at various neonatal time points to assess the development of the SSCC. Measurements of SSCC diameter were made on paint-perfused specimens at postnatal day (P) 0, P7, P10, and P14. Histologic evaluation of the SSCC was made on hematoxylin-eosin-stained sections at P10. RESULTS: A dysmorphic constriction of the superior arc of the SSCC in Brn4 knockout mice was initially detectable at P14. Interestingly, the mutant SSCC is indistinguishable from control mice at earlier neonatal time points. In mutant neonates, there is persistence of immature woven bone with high cellularity surrounding the perilymphatic space of the SSCC. These findings are not present in control animal specimens, which demonstrate appropriate lamellar bony architecture. CONCLUSIONS: In Brn4 knockout mice, constriction of the SSCC with narrowing of the bony labyrinth develops in the postnatal period at approximately P14. The persistence of immature bone in affected mice indicates that signaling abnormalities disrupt normal mesenchymal differentiation in the SSCC.

Animals↗
PubMed1989

Firearm ownership among nonurban adolescents.

Firearm injury is the second leading cause of death among teenagers. In this study we examined firearm acquisition and ownership in a biracial cohort of 664 teenagers (313 male and 351 female). Ownership was prevalent among male adolescents (48%) and rare among female adolescents (4%). Among these suburban and rural teenagers, the ownership rate was highest for white male adolescents (56%). Handgun ownership was more frequent among male school dropouts (22%) than enrollees (7%). The first firearm was typically acquired by late childhood or early adolescence (median age, 12.5 years). An adult male family member (eg, father, grandfather, uncle) was the primary source. The prevalence, developmental timing, and sociodemographic correlates of firearm acquisition should be useful for informing preventive clinical practice and interventions.

Adolescent↗
PubMed1997

Genotype-phenotype correlation in two sets of monozygotic twins with Williams syndrome.

We report on two sets of monozygotic (MZ) twins with Williams syndrome (WS), following the 6 pairs already reported in the literature. We have confirmed monozygosity of both pairs of twins by DNA microsatellite analysis and the clinical diagnosis by fluorescence in situ hybridization using a WS-specific probe. Analysis of the concordance of different clinical signs between members of each pair of twins benefitted from a lengthy clinical follow-up, from 24 months to 7 years in one pair, and from the age of 15 years with reevaluation after 2 years in the other pair. Most clinical signs were concordant in the twins of each pair, with differences present at younger ages, mainly minor facial anomalies, being attenuated with time. Developmental delay was substantially concordant, but the degree differed slightly between twins in each pair. Inguinal hernia was present in a single twin in pair 1. Facial anomalies and other signs attributable to connective tissue abnormalities were also displayed by only one twin in both sets, suggesting that the WS genotype has only a predisposing role in the development of these signs.

Adolescent↗
PubMed1996

Chondroitin sulfate proteoglycans in the developing central nervous system. II. Immunocytochemical localization of neurocan and phosphacan.

Using immunocytochemistry, we have compared the distribution of neurocan and phosphacan in the developing central nervous system. At embryonic day 13 (E13), phosphacan surrounds the radially oriented neuroepithelial cells of the telencephalon, whereas neurocan staining of brain parenchyma is very weak. By E16-19, strong staining of both neurocan and phosphacan is seen in the marginal zone and subplate of the neocortex, and phosphacan is present in the ventricular zone and also has a diffuse distribution in other brain areas. Phosphacan is also widely distributed in embryonic spinal cord, where it is strongly expressed throughout the gray and white matter, in the dorsal and ventral nerve roots, and in the roof plate at E13, when neurocan immunoreactivity is seen only in the mesenchyme of the future spinal canal. Neurocan first begins to appear in the spinal cord at E16-19, in the region of ventral motor neurons. In early postnatal and adult cerebellum, neurocan immunoreactivity is seen in the prospective white matter and in the granule cell, Purkinje cell, and molecular layers, whereas phosphacan immunoreactivity is associated with Bergmann glial fibers in the molecular layer and their cell bodies (the Golgi epithelial cells) below the Purkinje cells. These immunocytochemical results demonstrate that the expression of neurocan and phosphacan follow different developmental time courses not only in postnatal brain (as previously demonstrated by radioimmunoassay) but also in the embryonic central nervous system. The specific localization and different temporal expression patterns of these two proteoglycans are consistent with other evidence indicating that they have overlapping or complementary roles in axon guidance, cell interactions, and neurite outgrowth during nervous tissue histogenesis.

Animals↗
PubMed1996

Neurochemical development of the hippocampal region in the fetal rhesus monkey, III: calbindin-D28K, calretinin and parvalbumin with special mention of cajal-retzius cells and the retrosplenial cortex.

In spite of continuing controversy on the precise function of the calcium-binding proteins expressed in the hippocampal formation, nothing is known about their prenatal development in primates. In this study, calbindin-D28K, calretinin, and parvalbumin were localized in the hippocampal formation of seven rhesus monkey fetuses aged E47 to E90 (term 165 days). All of the three markers were expressed during the first half of gestation in distinct subsets of nonpyramidal neurons: calretinin-containing cells were the most numerous and relatively differentiated contrasting with a more restricted, less mature, parvalbumin-labeled population and a poor calbindin-positive nonpyramidal contingent. The granule cells and pyramidal neurons were calbindin-positive, including the pyramids of CA3 and the subicular complex, in contrast to the situation found in the adult monkey. The presubiculum and retrosplenial cortex, whose merging formed the caudal pole of the hippocampal formation, also expressed precociously the three calcium-binding proteins. A heterogeneous population of Cajal-Retzius-like cells was demonstrated in the marginal zone of the ventral hippocampal formation. The majority co-expressed calbindin-D28K and calretinin and displayed acetylcholinesterase activity but no GABA-like immunoreactivity. Major intrinsic and extrinsic pathways of the hippocampal system (mossy fiber system, alveus, fimbria, angular, and cingular bundles) were immunoreactive for calretinin and/or calbindin. The distinct developmental time course and regional pattern of distribution of calbindin-D28K, calretinin, and parvalbumin in the nonprincipal neurons suggests a precocious but asynchronous prenatal development of different inhibitory circuits in the hippocampal formation of primates. The labeling of several fiber systems in keeping with comparable early events in the entorhinal cortex (Berger et al.: Hippocampus 3:279-305, 1993), suggests the possibility of earlier functional circuits than hitherto inferred from the observations available in rodents, a hypothesis that deserves further investigation.

Animals↗