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Ivan Rodriguez

Publications and source records attributed to Ivan Rodriguez.

14 recordsLinked to original sources
PubMed2006

Projection of the Grüneberg ganglion to the mouse olfactory bulb.

In mammals, sensory neurons from the main olfactory and vomeronasal systems project their axons to the olfactory bulbs in the brain. We here report that a cluster of neurons, distinct from these two systems, located at the very tip of the mouse nose and called the Grüneberg ganglion expresses the mature olfactory-sensory neuron-specific marker olfactory marker protein (OMP), but is unlikely to express known odorant or pheromone receptors. The ganglion is present at birth and maintained during adult life. Tracing experiments indicate that these neurons target ipsilaterally to a specific set of glomeruli located on the caudal part of the olfactory bulb, and that this connection is necessary for the survival of the ganglion. The glomerular targets are structures previously proposed to be associated with suckling behaviour. These observations strongly suggest that this peculiar olfactory neuronal population plays a sensory role, possibly linked to chemoperception.

Amino Acids↗
PubMed2005

Olfactory expression of a single and highly variable V1r pheromone receptor-like gene in fish species.

Sensory neurons expressing members of the seven-transmembrane V1r receptor superfamily allow mice to perceive pheromones. These receptors, which exhibit no sequence homology to any known protein except a weak similarity to taste receptors, have only been found in mammals. In the mouse, the V1r repertoire contains >150 members, which are expressed by neurons of the vomeronasal organ, a structure present exclusively in some tetrapod species. Here, we report the existence of a single V1r gene in multiple species of a non-terrestrial, vomeronasal organ-lacking taxon, the teleosts. In zebrafish, this V1r gene is expressed in chemosensory neurons of the olfactory rosette with a punctate distribution, strongly suggesting a role in chemodetection. This unique receptor gene exhibits a remarkably high degree of sequence variability between fish species. It likely corresponds to the original V1r present in the common ancestor of vertebrates, which led to the large and very diverse expansion of vertebrate pheromone receptor repertoires, and suggests the presence of V1rs in multiple nonmammalian phyla.

Amino Acid Sequence↗
PubMed2004

Axon guidance of mouse olfactory sensory neurons by odorant receptors and the beta2 adrenergic receptor.

Odorant receptors (ORs) provide the core determinant of identity for axons of olfactory sensory neurons (OSNs) to coalesce into glomeruli in the olfactory bulb. Here, using gene targeting in mice, we examine how the OR protein determines axonal identity. An OR::GFP fusion protein is present in axons, consistent with a direct function of ORs in axon guidance. When the OR coding region is deleted, we observe OSNs that coexpress other ORs that function in odorant reception and axonal identity. It remains unclear if such coexpression is normally prevented by negative feedback on OR gene choice. A drastic reduction in OR protein level produces axonal coalescence into novel, remote glomeruli. By contrast, chimeric ORs and ORs with minor mutations perturb axon outgrowth. Strikingly, the beta2 adrenergic receptor can substitute for an OR in glomerular formation when expressed from an OR locus. Thus, ORs have not evolved a unique function in axon guidance.

Alleles↗
PubMed2004

Synthesis of mono- and bisdihydrodipyridopyrazines and assessment of their DNA binding and cytotoxic properties.

Aminoalkyl-substituted monomeric and dimeric dihydrodipyridopyrazines have been synthesized and evaluated as antitumor agents. Potent cytotoxic compounds were identified in both series. Biochemical and biophysical studies indicated that all these compounds strongly stabilized the duplex structure of DNA and some of them elicited a selectivity for GC-rich sequences. Sequence recognition by of the dimeric dihydrodipyridopyrazines is reminiscent of that of certain antitumor bisnaphthalimides. Compared to monomers, corresponding dimeric derivatives showed higher affinity for DNA. This property was attributed to a bisintercalative binding to DNA. This assumption was indirectly probed by electric linear dichroism and DNA relaxation experiments. DNA provides a bioreceptor for these dihydrodipyridopyrazine derivatives, but no poisoning of human topoisomerases I or II was detected. Most of the compounds efficiently inhibited the growth of L1210 murine leukemia cells and perturbed the cell cycle progression (with a G2/M block in most cases). A weak but noticeable in vivo antitumor activity was observed with one of the dimeric compounds. This studies identifies monomeric and dimeric dihydrodipyridopyrazines as a new class of DNA-targeted antitumor agents.

Animals↗
PubMed2004

Odorant and vomeronasal receptor genes in two mouse genome assemblies.

Odorant receptors (ORs) and vomeronasal receptors (V1Rs and V2Rs) are large superfamilies of chemosensory receptors. As an extension of previous research using the 2001 Celera mouse genome assembly, we analyzed OR and V1R genes in the 2002 public mouse genome assembly. We identified 1403 OR genes (1068 potentially intact) and 332 V1R genes (164 potentially intact) in this C57BL/6J mouse genome. This expands the mouse OR and V1R superfamilies by adding approximately 100 OR and approximately 40 V1R potentially intact genes. The description of the genomic distribution of OR genes is more complete and accurate, and two major errors in OR gene distribution in the 2001 Celera assembly were corrected. For the first time, the complete genomic distribution of V1R genes was investigated in detail and placed in context with that of OR genes. V1R genes, like OR genes, tend to form clusters of similar genes in the genome. Comparison between the two genome assemblies revealed a high rate of single-nucleotide polymorphisms (SNPs) in both OR and V1R genes. The high ratio of nonsynonymous SNPs over synonymous SNPs in V1R genes suggests positive selection for these genes, possibly favoring species-specific and strain-specific pheromone detection. In addition, detailed analysis of the SNP rate aided in the identification of key residues in ORs.

Animals↗
PubMed2004

Pheromone receptors in mammals.

In most mammals, pheromone perception mediates intraspecies interactions related to reproduction, such as mate recognition, intermale aggressive behaviors, or exchanges between females and their offspring. Recent molecular findings, particularly the identification of two large pheromone receptor gene superfamilies, provide today invaluable tools to better understand the way mammals make sense of pheromonal information.

Animals↗
PubMed2002

A divergent pattern of sensory axonal projections is rendered convergent by second-order neurons in the accessory olfactory bulb.

The mammalian vomeronasal system is specialized in pheromone detection. The neural circuitry of the accessory olfactory bulb (AOB) provides an anatomical substrate for the coding of pheromone information. Here, we describe the axonal projection pattern of vomeronasal sensory neurons to the AOB and the dendritic connectivity pattern of second-order neurons. Genetically traced sensory neurons expressing a given gene of the V2R class of vomeronasal receptors project their axons to six to ten glomeruli distributed in globally conserved areas of the AOB, a theme similar to V1R-expressing neurons. Surprisingly, second-order neurons tend to project their dendrites to glomeruli innervated by axons of sensory neurons expressing the same V1R or the same V2R gene. Convergence of receptor type information in the olfactory bulb may represent a common design in olfactory systems.

Animals↗
PubMed2002

Deficient pheromone responses in mice lacking a cluster of vomeronasal receptor genes.

The mammalian vomeronasal organ (VNO), a part of the olfactory system, detects pheromones--chemical signals that modulate social and reproductive behaviours. But the molecular receptors in the VNO that detect these chemosensory stimuli remain undefined. Candidate pheromone receptors are encoded by two distinct and complex superfamilies of genes, V1r and V2r (refs 3 and 4), which code for receptors with seven transmembrane domains. These genes are selectively expressed in sensory neurons of the VNO. However, there is at present no functional evidence for a role of these genes in pheromone responses. Here, using chromosome engineering technology, we delete in the germ line of mice an approximately 600-kilobase genomic region that contains a cluster of 16 intact V1r genes. These genes comprise two of the 12 described V1r gene families, and represent approximately 12% of the V1r repertoire. The mutant mice display deficits in a subset of VNO-dependent behaviours: the expression of male sexual behaviour and maternal aggression is substantially altered. Electrophysiologically, the epithelium of the VNO of such mice does not respond detectably to specific pheromonal ligands. The behavioural impairment and chemosensory deficit support a role of V1r receptors as pheromone receptors.

Aggression↗
PubMed2002

Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice.

The mammalian olfactory system consists of two anatomically segregated structures, the main olfactory system and the vomeronasal system, which each detect distinct types of chemical stimuli in the environment. During development, sensory neurons establish precise axonal connections with their respective targets within the olfactory bulb. The specificity of the odorant or vomeronasal receptor expressed by the sensory neuron is crucial in this process, yet it is less clear which of the more conventional axon guidance molecules are involved. Here, we show that neuropilin-2, a coreceptor for some of the class 3 semaphorins, is expressed in subpopulations of olfactory and vomeronasal sensory neurons. We generated a knock-out mutation in the neuropilin-2 gene by gene targeting in embryonic stem cells. Neuropilin-2 mutant mice exhibit profound and distinct effects on target innervation within the olfactory bulb. In the main olfactory system, axons of olfactory sensory neurons penetrate into the deeper layers of the main olfactory bulb. In the vomeronasal system, axonal fasciculation within the vomeronasal nerve is affected; some axons are misrouted and innervate glomeruli in an ectopic domain of the accessory olfactory bulb.

Animals↗
PubMed2002

Multiple new and isolated families within the mouse superfamily of V1r vomeronasal receptors.

Seven-transmembrane-domain proteins encoded by the vomeronasal receptor V1r and V2r gene superfamilies, and expressed by vomeronasal sensory neurons, are believed to be pheromone receptors in rodents. Four V1r gene families have been described in the mouse (V1ra, V1rb, V1rc and V3r). Here we have screened near-complete mouse genomic databases to obtain a first global draft of the mouse V1r repertoire, including 104 new V1r genes. It comprises eight new and extremely isolated families in addition to the four families previously identified. Members of these new families were expressed in vomeronasal sensory neurons. The genome-wide view revealed great sequence diversity within the V1r superfamily. Phylogenetic analyses suggested an ancient original radiation, followed by the isolation, divergence and expansion of families by extensive gene duplications and frequent gene loss. The isolated nature of these gene families probably reflects a specialization of different receptor classes in the detection of specific types of chemicals.

Animals↗