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Biomedical subjects

L Puelles

Publications and source records attributed to L Puelles.

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

Cadherin expression in the retina and retinofugal pathways of the chicken embryo.

The expression of two calcium-dependent adhesion molecules of the cadherin superfamily (cadherin-6B and cadherin-7) was mapped in the embryonic neural retina and retinofugal pathways of the chicken embryo and compared with the expression of R-cadherin, N-cadherin, and B-cadherin, studied previously. Whereas B-cadherin is only found in Miller glia, the other four cadherins are each expressed by specific subpopulations of retinal neurons. For example, different (but partly overlapping) populations of bipolar cells express R-cadherin, cadherin-6B, and cadherin-7. Cadherin-6B and cadherin-7 are also expressed by subsets of amacrine cells. In the inner plexiform layer, cadherin-6B and cadherin-7 immunoreactivities are restricted to specific sublaminae associated with synapsin-I-positive nerve terminals. In addition, cadherin-6B and cadherin-7 are expressed by a subset of ganglion cells that project to several retinorecipient nuclei forming part of the accessory optic system (e.g., nucleus of the basal optic root and external pretectal nucleus). Together with their connecting fiber tracts, these nuclei also express cadherin-6B and cadherin-7 in their neurons and neuropile. The expression patterns of the two cadherins overlap but show distinct differences. Some other visual nuclei express cadherin-7 but not cadherin-6B. The expression patterns differ from those previously described for N- and R-cadherin. Together, these results demonstrate that cadherins could provide a system of adhesive cues that specify developing retinal circuits and other functional connections and subsystems in the embryonic chicken visual system.

Animals↗
PubMed1998

Early neuromeric distribution of tyrosine-hydroxylase-immunoreactive neurons in human embryos.

A segmental mapping of brain tyrosine-hydroxylase-immunoreactive (TH-IR) neurons in human embryos between 4.5 and 6 weeks of gestation locates with novel precision the dorsoventral and anteroposterior topography of the catecholamine-synthetizing primordia relative to neuromeric units. The data support the following conclusions. (1) All transverse sectors of the brain (prosomeres in the forebrain, midbrain, rhombomeres in the hindbrain, spinal cord) produce TH-IR neuronal populations. (2) Each segment shows peculiarities in its contribution to the catecholamine system, but there are some overall regularities, which reflect that some TH-IR populations develop similarly in different segments. (3) Dorsoventral topology of the TH-IR neurons indicates that at least four separate longitudinal zones (in the floor and basal plates and twice in the alar plate) found across most segments are capable of producing the TH-IR phenotype. (4) Basal plate TH-IR neurons tend to migrate intrasegmentally to a ventrolateral superficial position, although some remain periventricular; those in the brainstem are related to motoneurons of the oculomotor and branchiomotor nuclei. (5) Some alar TH-IR populations migrate superficially within the segmental boundaries. (6) Most catecholaminergic anatomical entities are formed as fusions of smaller segmental components, each of which show similar histogenetic patterns. A nomenclature is proposed that partly adheres to previous terminology but introduces the distinction of embryologically different cell populations and unifies longitudinally analogous entities. Such a model, as presented in the present study, is convenient for resolving problems of homology of the catecholamine system across the diversity of vertebrate forms.

Body Patterning↗
PubMed1998

Expression pattern of cSix3, a member of the Six/sine oculis family of transcription factors.

We describe the expression pattern of cSix3, a chick homologue of the murine Six3. cSix3 transcripts are expressed from presomitic stages in the most anterior portion of the neural plate. As the neural tube folds and the optic vesicles evaginate, cSix3 is expressed in the optic vesicle and the rostroventral forebrain. At later stages, cSix3 is found in most of the structures derived from the anterior neural plate, i.e. olfactory epithelium, septum, adenohypophysis, hypothalamus and preoptic areas. During eye development, cSix3 expression is first found in the entire optic vesicle and the overlying ectoderm but soon becomes restricted to the prospective neural retina and to the lens placode. In the developing neural retina, cSix3 is expressed in the entire undifferentiated neuroepithelium but is rapidly downregulated, first in the postmitotic photoreceptors and later in the majority of retinal ganglion cells.

Animals↗
PubMed1998

Regionalization of the prosencephalic neural plate.

Recent embryological studies are beginning to establish that the underlying organization of the forebrain may be reduced to relatively simple elements that are common to all vertebrates. We begin this chapter by reviewing studies that describe the similarities in prospective fate and molecular organization of the developing neural plate in fish, frogs, chickens, and mice. The chapter next addresses mechanisms that regulate regional specification in the anterior central nervous system. There is now evidence that the axial mesendoderm anterior to the notochord (the prechordal plate) has a central role in induction of the floor and basal plate primordia (hypothalamus) of the forebrain. Patterning of the anterolateral neural plate (telencephalon) may be regulated by FGF8 produced in the anterior neural ridge. Thus, the synthesis of information from fate mapping and experimental embryological and genetic studies is illuminating the mechanisms that generate the different components of the forebrain.

Animals↗
PubMed1998

Importance of immunological and inflammatory processes in the pathogenesis and therapy of Alzheimer's disease.

The contribution of autoimmune processes or inflammatory components in the etiology and pathogenesis of Alzheimer's disease (AD) has been suspected for many years. The presence of antigen-presenting, HLA-DR-positive and other immunoregulatory cells, components of complement, inflammatory cytokines and acute phase reactants have been established in tissue of AD neuropathology. Although these data do not confirm the immune response as a primary cause of AD, they indicate involvement of immune processes at least as a secondary or tertiary reaction to the preexisting pathogen and point out its driving-force role in AD pathogenesis. These processes may contribute to systemic immune response. Thus, experimental and clinical studies indicate impairments in both humoral and cellular immunity in an animal model of AD as well as in AD patients. On the other hand, anti-inflammatory drugs applied for the treatment of some chronic inflammatory diseases have been shown to reduce risk of AD in these patients. Therefore, it seems that anti-inflammatory drugs and other substances which can control the activity of immunocompetent cells and the level of endogenous immune response can be valuable in the treatment of AD patients.

Acute-Phase Proteins↗
PubMed1997

Patterns of gene expression in the neural plate and neural tube subdivide the embryonic forebrain into transverse and longitudinal domains.

The analysis of gene expression patterns in the neural plate and neural tube of the embryonic mouse forebrain shows that, at its earliest stages, the neuroepithelium is subdivided into molecularly distinct domains. Here, and in previous publications, we provide evidence that the patterns of gene expression can be related to primary morphogenetic processes that organize the histological primordia of the embryonic central nervous system into longitudinal and transverse domains. Longitudinal domains are generated by dorsoventral patterning signals produced by the axial mesendoderm and nonneural ectoderm. Transverse domains (proneuromeres and neuromeres) expressing distinct combinations of genes are present in the neural plate and neural tube.

Animals↗
PubMed1997

Retrospective clonal analysis of the cerebellum using genetic laacZ/lacZ mouse mosaics.

Analysis of lacZ neuronal clones in the mouse cerebellum demonstrates genealogical independence of the primary and secondary germinal epithelia (PGE and SGE) from early development. PGE precursors and their neuronal descendants are organised into two polyclonal groups of similar sizes that exhibit parasagittal patterning and generally respect the midline. The relationship between these two groups cannot be traced back in time to less than 80 independent cells, which were probably recruited following a period of non-coherent growth that distributes unrelated cells into distinct territories of the neural tube. A lateromedial clonal organisation is observed in the mature cerebellum, suggesting the existence of many small parasagittal domains of clonal restriction and/or of cell dispersion in the rostrocaudal but not in the mediolateral dimension. The organisation is orthogonal with respect to the cellular organisation in the neural tube as is the genetic organisation. Cellular and genetic patterning of the cerebellum therefore share similarities. A possible hypothesis is that distinct cell behaviours create the different clonal domains observed in this study and that the cellular and genetic organisation of the cerebellum are coordinated.

Animals↗
PubMed1996

The avian inferior olive derives from the alar neuroepithelium of the rhombomeres 7 and 8: an analysis by using chick-quail chimeric embryos.

Homotopic and isochronic transplantation of the alar plate of the rhombomeres 7 and 8 was performed between chick and quail embryos at the stage of 10-14 somites. Analysis of the graft derivatives in 12-day-old chimeric embryos by means of the quail nucleolar marker showed that the ipsilateral inferior olive is formed from the transplanted neuroepithelium. In all embryos some cells originating from the graft were also found scattered throughout the contralateral inferior olive. The present results demonstrate that the inferior olive derives from the alar plate of the rhombomeres 7 and 8 and support the notion that a small contingent of inferior olivary neurones crosses the interolivary commissure during development.

Animals↗
PubMed1996

Intertectal commissural projection in the lizard Gallotia stehlini: origin and midline topography.

The retinotectal projection of reptiles is largely crossed. The intertectal commissure is an important pathway that interconnects directly the two sides of the optic tectum. The rostrocaudal topography of intertectal commissural fibers at the dorsal midplane was examined by means of the in vitro horseradish peroxidase (HRP) labelling technique in the lizard Gallotia stehlini. Unilateral large deposits of tracer in the optic tectum as well as smaller deposits restricted to one quadrant were used to map the intertectal fibers anterogradely. Most commissural axons reached the contralateral side grouped into a dense bundle at the transition between two structurally distinct parts of the midbrain dorsal midline. The smaller rostral zone relates laterally to the griseum tectale, whereas the larger caudal zone relates to the tectum. The intertectal fibers seem to converge on the rostralmost part of the latter midline region, even though they originate throughout the optic tectum. A rough rostrocaudal tectotopic order was detected at the midline. Retrogradely labelled neurons were best obtained by depositing HRP directly within the compact commissure at the midline. These belong to pyriform cells in the periventricular layers 3 and 5. Axons labelled from the tectum did not enter the posterior commissure nor the intervening commissural region related to the griseum tectale.

Animals↗
PubMed1996

Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of Down syndrome.

The single-minded (sim) gene encodes a transcriptional regulator that functions as a key determinant of central nervous system (CNS) midline development in Drosophila. We report here the identification of two murine homologs of sim, Sim1 and Sim2, whose products show a high degree of sequence conservation with Drosophila SIM in their amino-terminal halves, with each containing a basic helix-loop-helix domain as well as a PAS domain. Sim1 maps to the proximal region of mouse chromosome 10, whereas Sim2 maps to a portion of the distal end of chromosome 16 that is syntenic to the Down syndrome critical region of human chromosome 21. Recent exon-trapping studies have identified in the critical region several exons of a human sim homolog which appears to be the homolog of murine Sim2; this has led to the hypothesis that increased dosage of this sim homolog in cases of trisomy 21 might be a causal factor in the pathogenesis of Down syndrome. We have examined the expression patterns of the Sim genes during embryogenesis. Both genes are expressed in dynamic and selective fashion in specific neuromeric compartments of the developing forebrain, and the expression pattern of Sim2 provides evidence for early regionalization of the diencephalon prior to any overt morphological differentiation in this region. Outside the CNS, Sim1 is expressed in mesodermal and endodermal tissues, including developing somites, mesonephric duct, and foregut. Sim2 is expressed in facial and trunk cartilage, as well as trunk muscles. Both murine Sim genes are also expressed in the developing kidney. Our data suggest that the Sim genes play roles in directing the regionalization of tissues where they are expressed. Moreover, the expression pattern documented for Sim2 may provide insights into its potential roles in Down syndrome.

Amino Acid Sequence↗
PubMed1996

A segmental map of architectonic subdivisions in the diencephalon of the frog Rana perezi: acetylcholinesterase-histochemical observations.

The work examines frog diencephalic subdivisions from a segmental viewpoint and adds a number of details to the atlas of the bullfrog diencephalon reported by Neary and Northcutt [1983]. Acetylcholinesterase histochemistry was performed on brains of Rana perezi, sectioned either sagittally or in a plane roughly parallel to the optic tract to optimize detection of segmented landmarks. This material provided a very detailed picture of individual neurons, neuropils and some fiber tracts expressing the enzyme in diverse patterns characteristic for each diencephalic region. The main diencephalic areas previously recognized in the bullfrog appeared subdivided into smaller AChE-chemoarchitectonic units. Modified subdivisions are proposed for several entities: preoptic, suprachiasmatic, entopeduncular, ventral thalamic, anterior thalamic, pretectal, hypothalamic and tuberculum posterior regions. A number of cell groups are described for the first time in frogs. This mapping is expected to be useful for the interpretation of immunocytochemical and experimental hodologic results in the diencephalon of frogs and opens new possibilities for comparative analysis.

Acetylcholinesterase↗
PubMed1995

Morphological fate of rhombomeres in quail/chick chimeras: a segmental analysis of hindbrain nuclei.

Quail rhombomeres two to six (r2-r6) were individually grafted homotopically into the hindbrain of chick embryos at 2 days of incubation. Nine to 10 days after the operation the chimeric embryos were fixed and processed for parallel cytoarchitectural and immunocytochemical study (with an anti-quail antibody) in order to map the anatomical fate of the grafted tissue. Emphasis was placed on conventionally identified and distinct neuronal populations composing the sensory and motor longitudinal columns. Grafted rhombomeres consistently developed as complete transverse slices of the chimeric hindbrain. Interrhombomeric cell migration was either sparse or restricted to specific nuclei. The cranial nerve motor nuclei showed rhombomeric origins consistent with the patterns described in early embryos. Unexpectedly, alar r2 was found to form the auricular part of the cerebellum. As regards the cochlear nuclei, we found that nucleus angularis derives from r3 to r6, nucleus laminaris from r5 to r6, nucleus magnocellularis from r6 to r7 and nucleus olivaris superior from r5. The nuclei of the lateral lemniscus originated between r1 and r3. We also delimited the respective rhombomeric subdivisions of the sensory vestibular and trigeminal columns, both of which extend from r1 caudalwards throughout the hindbrain. There were consistently some interrhombomeric neuronal migrations inside the vestibular column, some motor nuclei and the reticular formation, involving only one rhombomere length. The pontine nuclei, which extended from r1 to r7, showed neuronal migrations that crossed several rhombomeres. On the whole, these results represent the first anatomical analysis of the mature avian hindbrain in terms of rhombomere-derived domains.

Animals↗
PubMed1995

Id gene expression during development and molecular cloning of the human Id-1 gene.

Id genes encode helix-loop-helix proteins that inhibit transcription by forming inactive heterodimers with basic helix-loop-helix (bHLH) proteins. bHLH proteins normally form either homodimers or heterodimers with other bHLH proteins and bind to a DNA sequence element activating transcription. Id-containing heterodimers are inactive because Id proteins lack the basic amino acid region necessary to form a DNA-binding domain. We have examined the relative levels of Id-1 and Id-2 mRNA during normal development and in malignant tissues. In the course of these experiments we cloned and sequenced the human Id-1 cDNA. Two related cDNA molecules encoding human Id-1 mRNAs were identified. Id-1a is a cDNA of 958 nucleotides and can encode a protein of 135 amino acids. Id-1b cDNA is 1145 nucleotides, can encode a protein of 149 amino acids, and appears to be a splice variant of Id-1a. The amino acid sequence of human Id-1 is greater than 90% homologous to that of mouse Id-1. The patterns of Id-1 and Id-2 expression during mouse development vary widely, and we detected Id-1 expression in human fetal and adult tissues from lung, liver, and brain. High Id-1 mRNA expression was found in many human tumor cell lines, including those isolated from nervous system tumors. We mapped Id-2 to human chromosome 2p25.

Amino Acid Sequence↗
PubMed1995

T-brain-1: a homolog of Brachyury whose expression defines molecularly distinct domains within the cerebral cortex.

The mechanisms that regulate regional specification and evolution of the cerebral cortex are obscure. To this end, we have identified and characterized a novel murine and human gene encoding a putative transcription factor related to the Brachyury (T) gene that is expressed only in postmitotic cells. T-brain-1 (Tbr-1) mRNA is largely restricted to the cerebral cortex, where during embryogenesis it distinguishes domains that we propose may give rise to paleocortex, limbic cortex, and neocortex. Tbr-1 and Id-2 expression in the neocortex have discontinuities that define molecularly distinct neocortical areas. Tbr-1 expression is analyzed in the context of the prosomeric model. Topological maps are proposed for the organization of the dorsal telencephalon.

Amino Acid Sequence↗
PubMed1995

Induction of ectopic engrailed expression and fate change in avian rhombomeres: intersegmental boundaries as barriers.

We tested the possibility of inducing ectopic expression of the gene Engrailed-2 (En-2) in the rhombomeres of the 2-days-old chick embryo. The experimental procedure consisted of grafting En-2-expressing neuroepithelium (prospective isthmocerebellum) from a quail or a mouse embryo into different rostrocaudal levels in the hindbrain of a host chick embryo. The graft replaced a given excised host rhombomere, the rostral and caudal limits of which were either also excised or left intact in different experiments. Induction of En-2 occurred in the host hindbrain, but only when the graft did not contact with host interrhombomeric boundaries and only in the alar plate of the rhombomeres immediately contacting the graft. Long survival experimental embryos showed that induced rhombomeres give rise to a cerebellar phenotype in their transformed alar plates. We thus demonstrate here a pluripotential state of the early rhombomeres as well as a possible role of the interrhombomeric limits as barriers to morphogenetic influences.

Animals↗
PubMed1995

A segmental morphological paradigm for understanding vertebrate forebrains.

The idea is presented that modern segmental thinking on the forebrain is best conceived of as a scientific paradigm, which is revealing itself to be increasingly advantageous for the interpretation of both causal developmental/genetic data and pitfall-free morphology. Various related or opposed viewpoints are considered briefly, emphasizing their respective assumptions with regard to longitudinal and transverse subdivisions.

Animals↗