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C Dulac

Publications and source records attributed to C Dulac.

At least 19 recordsLinked to original sources

TRP2: a candidate transduction channel for mammalian pheromone sensory signaling.

The vomeronasal organ (VNO) of terrestrial vertebrates plays a key role in the detection of pheromones, chemicals released by animals that elicit stereotyped sexual and aggressive behaviors among conspecifics. Sensory transduction in the VNO appears unrelated to that in the vertebrate olfactory and visual systems: the putative pheromone receptors of the VNO are evolutionarily independent from the odorant receptors and, in contrast to vertebrate visual and olfactory transduction, vomeronasal transduction is unlikely to be mediated by cyclic-nucleotide-gated channels. We hypothesized that sensory transduction in the VNO might instead involve an ion channel of the transient receptor potential (TRP) family, members of which mediate cyclic-nucleotide-independent sensory responses in Drosophila melanogaster and Caenorhabditis elegans and play unknown functions in mammals. We have isolated a cDNA (rTRP2) from rat VNO encoding a protein of 885 amino acids that is equally distant from vertebrate and invertebrate TRP channels (10-30% amino acid identity). rTRP2 mRNA is exclusively expressed in VNO neurons, and the protein is highly localized to VNO sensory microvilli, the proposed site of pheromone sensory transduction. The absence of Ca2+ stores in sensory microvilli suggests that, in contrast to a proposed mechanism of activation of mammalian TRP channels, but in accord with analysis of TRP function in Drosophila phototransduction, the gating of TRP2 is independent from the depletion of internal Ca2+ stores. Thus, TRP2 is likely to participate in vomeronasal sensory transduction, which may share additional similarities with light-induced signaling in the Drosophila eye.

Amino Acid Sequence

A map of pheromone receptor activation in the mammalian brain.

In mammals, the detection of pheromones is mediated by the vomeronasal system. We have employed gene targeting to visualize the pattern of projections of axons from vomeronasal sensory neurons in the accessory olfactory bulb. Neurons expressing a specific receptor project to multiple glomeruli that reside within spatially restricted domains. The formation of this sensory map in the accessory olfactory bulb and the survival of vomeronasal organ sensory neurons require the expression of pheromone receptors. In addition, we observe individual glomeruli in the accessory olfactory bulb that receive input from more than one type of sensory neuron. These observations indicate that the organization of the vomeronasal sensory afferents is dramatically different from that of the main olfactory system, and these differences have important implications for the logic of olfactory coding in the vomeronasal organ.

Animals

Molecular identity of hematopoietic precursor cells emerging in the human embryo.

It is now accepted from studies in animal models that hematopoietic stem cells emerge in the para-aortic mesoderm-derived aorta-gonad-mesonephros region of the vertebrate embryo. We have previously identified the equivalent primitive hematogenous territory in the 4- to 6-week human embryo, under the form of CD34(+)CD45(+)Lin- high proliferative potential hematopoietic cells clustered on the ventral endothelium of the aorta. To characterize molecules involved in initial stem cell emergence, we first investigated the expression in that territory of known early hematopoietic regulators. We herein show that aorta-associated CD34(+) cells coexpress the tal-1/SCL, c-myb, GATA-2, GATA-3, c-kit, and flk-1/KDR genes, as do embryonic and fetal hematopoietic progenitors later present in the liver and bone marrow. Next, CD34(+)CD45(+) aorta-associated cells were sorted by flow cytometry from a 5-week embryo and a cDNA library was constructed therefrom. Differential screening of that library with total cDNA probes obtained from CD34(+) embryonic liver cells allowed the isolation of a kinase-related sequence previously identified in KG-1 cells. In addition to emerging blood stem cells, KG-1 kinase is also strikingly expressed in all developing endothelial cells in the yolk sac and embryo, which suggests its involvement in the genesis of both hematopoietic and vascular cell lineages in humans.

Antigens, CD34

Expression of candidate pheromone receptor genes in vomeronasal neurons.

In mammals, olfactory sensory perception is mediated by two anatomically and functionally distinct organs: the main olfactory epithelium (MOE) and the vomeronasal organ (VON). Pheromones activate the VNO and elicit a characteristic array of innate reproductive and social behaviors, along with dramatic neuroendocrine responses. Recent approaches have provided new insights into the molecular biology of sensory transduction in the VNO. Differential screening of cDNA libraries constructed from single sensory neurons from the rat VNO has led to the isolation of a family of genes which are likely to encode mammalian pheromone receptors. The isolation of these receptors from the VNO might permit the analysis of the molecular events which translate the bindings of pheromones into innate stereotypic behaviors and help to elucidate the logic of pheromone perception in mammals.

Amino Acid Sequence

A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution.

Mammals have retained two functionally and anatomically independent collections of olfactory neurons located in the main olfactory epithelium and in the vomeronasal organ (VNO). Pheromones activate the VNO in order to elicit fixed action behaviors and neuroendocrine changes involved in animal reproduction and aggression. Differential screening of cDNA libraries constructed from individual rat VNO neurons has led to the isolation of a novel family of approximately 100 genes encoding seven transmembrane receptors with sequence similarity with Ca2+-sensing and metabotropic glutamate receptors. These genes are likely to encode a novel family of pheromone receptors. Patterns of receptor gene expression suggest that the VNO is organized into discrete and sexually dimorphic functional units that may permit segregation of pheromone signals leading to specific arrays of behaviors and neuroendocrine responses.

Aging

Visualizing an olfactory sensory map.

We have developed a genetic approach to visualize axons from olfactory sensory neurons expressing a given odorant receptor, as they project to the olfactory bulb. Neurons expressing a specific receptor project to only two topographically fixed loci among the 1800 glomeruli in the mouse olfactory bulb. Our data provide direct support for a model in which a topographic map of receptor activation encodes odor quality in the olfactory bulb. Receptor swap experiments suggest that the olfactory receptor plays an instructive role in the guidance process but cannot be the sole determinant in the establishment of this map. This genetic approach may be more broadly applied to visualize the development and plasticity of projections in the mammalian nervous system.

Animals

A novel family of genes encoding putative pheromone receptors in mammals.

In mammals, olfactory sensory perception is mediated by two anatomically and functionally distinct sensory organs: the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). Pheromones activate the VNO and elicit a characteristic array of innate reproductive and social behaviors, along with dramatic neuroendocrine responses. Differential screening of cDNA libraries constructed from single sensory neurons from the rat VNO has led to the isolation of a family of about 30 putative receptor genes. Sequence analysis indicates that these genes comprise a novel family of seven transmembrane domain proteins unrelated to the receptors expressed in the MOE. Moreover, the expression of each member of the gene family is restricted to a small subpopulation of VNO neurons. These genes are likely to encode mammalian pheromone receptors.

Amino Acid Sequence

Negative regulation of Schwann cell myelin protein gene expression by the dorsal root ganglionic microenvironment.

In vivo, the surface glycoprotein Schwann cell myelin protein (SMP) is expressed in the quail peripheral nervous system exclusively by Schwann cells. It is not detectable at any developmental stage either in enteric glia or in ganglionic satellite cells. We demonstrate here that the satellite glial cells of the dorsal root ganglia start to express SMP on their surface when they are dissociated into single cells and cultivated in vitro. Activation of SMP synthesis is a rapid event observed in mass cultures of dorsal root ganglia dissociated cells as soon as 4 h after the onset of the culture. Confocal microscope analysis revealed that satellite cells may acquire the Schwann cell marker when still in close contact with the neuronal soma. Clonal cultures of satellite cells from E8 dorsal root ganglia demonstrated that the progeny of these SMP-negative cells steadily express SMP. This, together with similar results previously obtained with enteric glia, suggests that the SMP-positive phenotype is a constitutive trait of the peripheral glial cell lineage which is inhibited in satellite cells in vivo by the microenvironment prevailing in the peripheral nervous system ganglia.

Animals

Molecular characterization of the Schwann cell myelin protein, SMP: structural similarities within the immunoglobulin superfamily.

The Schwann cell myelin protein (SMP), previously defined in quail and chick by a monoclonal antibody, is in vivo exclusively expressed by myelinating and nonmyelinating Schwann cells and oligodendrocytes. The isolation of the complete nucleotide sequence of SMP is reported here. The predicted polypeptide chain reveals that SMP is a transmembrane molecule of the immunoglobulin superfamily showing sequence similarities with several surface glycoproteins expressed in the nervous and immune systems. In spite of a 43.5% overall sequence identity between rat myelin-associated glycoprotein (MAG) and quail SMP, SMP does not seem to be the avian homolog of MAG, since their expression, regulation, and functions are significantly different. Unusual sequence arrangements shared by SMP, MAG, and two lymphoid antigens suggest the existence of a particular subgroup in the immunoglobulin superfamily.

Amino Acid Sequence

Phenotypic plasticity of Schwann cells and enteric glial cells in response to the microenvironment.

We produced earlier a monoclonal antibody against Schwann cell myelin protein (SMP), a glycoprotein expressed on Schwann cells (SC) but not on satellite cells of the ganglia or enteric glial cells. We now studied whether SMP expression is environmentally regulated in the different compartments of the peripheral nervous system. Quail neural-crest cells from either mes-metencephalic, vagal, or truncal levels of the neuraxis were heterochronically associated with gut wall, skin, or muscle tissues from embryonic day (E) 7 to E11 chickens. Coculture of these chimeric organs revealed that as in normal development glial cells, characterized by HNK1 immunoreactivity and the quail nuclear marker, expressed the SMP phenotype exclusively in skin and muscle, failing to do so in gut. However, when SMP+ SC from quail sciatic nerves were cocultured with chicken gut, these cells rapidly lost their initial SMP immunoreactivity. In contrast, when associated with muscle and skin, SC remained SMP+, even in the complete absence of neuronal cells. Enteric plexuses from E8 to E15 quail gut express SMP+ and laminin when withdrawn from the intestinal-mesenchyme environment. These results show that SMP can be expressed by enteric glial cells and that the SC SMP phenotype is strongly inhibited by the gut-wall environment. Moreover, these results strongly suggest that these two types of glial cells belong to the same lineage and that their terminal phenotype is modulated through cell-to-cell interactions.

Animals

Glial cell lineages in the neural crest.

We have been studying how and when the different peripheral glial cell lineages individualize during avian embryonic development. Three different and complementary experimental approaches were used for this purpose: 1) the quail/chick chimera system allowed the tracing in vivo of the origin of the various types of peripheral glial cells (Schwann cells of nerves, satellite glial cells of sensory and autonomic ganglia, and enteric glial cells), and the analysis of the non-neuronal cell population of ganglia; 2) characterisation of early cell-type specific markers that discriminate between the different glial cell subpopulations; and 3) analysis of the progeny of neural crest cells in clonal cultures. As a result of these approaches, two novel glial-specific markers, expressed earlier than any previously described myelin components, have been identified and partly characterised. The divergence of glial and neuronal cell lineages is a process that is not completely terminated during the phase of neural crest migration. Whereas some cells are apparently already totally committed to a glial fate at this stage, others retain dual neuronal/glial potentialities.

Animals