Target-independent pattern specification in the olfactory epithelium

Sullivan, Stephen N.; Bohm, Staffan; Ressler, Kerry J.; Horowitz, Lisa F.; Buck, Linda B.

doi:10.1016/0896-6273(95)90170-1

Cited by 143 publications

(118 citation statements)

References 65 publications

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“…42 What happens after the genetic or surgical elimination of the OE? Odorant receptor gene expression by OSNs is completely independent of the OB, either in the absence of an OB during embryogenesis 43 or during regeneration after OSN lesion. 44,45 Neither total nor partial sensory olfactory deprivation (closure of the nostril by electrocauterization) in newborns has any apparent effect on the number of OSNs in the OE 46 (Table 1).…”

Section: Mutual Influences Between Oe and Obmentioning

confidence: 96%

The olfactory bulb as an independent developmental domain

López‐Mascaraque

Castro

2002

Cell Death Differ

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The olfactory system is a good model to study the mechanisms underlying guidance of growing axons to their appropriate targets. The formation of the olfactory bulb involves differentiation of several populations of cells and the initiation of the central projections, all under the temporal and spatial patterns of gene expression. Moreover, the nature of interactions between the olfactory epithelium, olfactory bulb and olfactory cortex at early developmental stages is currently of great interest. To explore these questions more fully, the present review aims to correlate recent data from different developmental studies, to gain insight into the mechanisms involved in the specification and development of the olfactory system. From our studies in the pax6 mutant mice (Sey Neu /Sey Neu ), it was concluded that the initial establishment of the olfactory bulb central projections is able to proceed independently of the olfactory sensory axons from the olfactory epithelium. The challenge that now remains is to consider the validity of the olfactory bulb as an independent development domain. In the course of evaluating these ideas, we will review the orchestra of molecular cues involved in the formation of the projection from the OB to the olfactory cortex.

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Section: Mutual Influences Between Oe and Obmentioning

confidence: 96%

The olfactory bulb as an independent developmental domain

López‐Mascaraque

Castro

2002

Cell Death Differ

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“…Neurogenesis of the OSNs continues into adulthood and is offset by programmed cell death (apoptosis) to maintain a constant thickness of the epithelium (Carr and Farbman, 1993;Mahalik, 1996;Fung et al, 1997;Voyron et al, 1999;Cowan and Roskams, 2004). Expression onsets of a small subset of ORs in the olfactory epithelium have been examined using in situ hybridization, revealing a time window between E11.5 and E14 (Strotmann et al, 1995;Sullivan et al, 1995;Saito et al, 1998). Because of the vast number of ORs expressed in the MOE, it is still elusive whether OSNs expressing different ORs have similar onsets and growth rates during development.…”

Section: Introductionmentioning

confidence: 99%

Differential development of odorant receptor expression patterns in the olfactory epithelium: A quantitative analysis in the mouse septal organ

Tian

2008

Developmental Neurobiology

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The rodent olfactory epithelium expresses more than 1000 odorant receptors (ORs) with distinct patterns, yet it is unclear how such patterns are established during development. In the current study, we investigated development of the expression patterns of different ORs in the septal organ, a small patch of olfactory epithelium predominantly expressing nine identified ORs. The presumptive septal organ first appears at about embryonic day 16 (E16) and it completely separates from the main olfactory epithelium (MOE) at about postnatal day 7 (P7). Using in situ hybridization, we quantified the densities of the septal organ neurons labeled by specific RNA probes of the nine abundant OR genes from E16 to postnatal 3 months. The results indicate that olfactory sensory neurons (OSNs) expressing different ORs have asynchronous temporal onsets. For instance, MOR256-17 and MOR236-1 cells are present in the septal organ at E16; however, MOR0-2 cells do not appear until P0. In addition, OSNs expressing different ORs show distinct developmental courses and reach their maximum densities at different stages ranging from E16 (e.g. MOR256-17) to 1 month (e.g. MOR256-3 and MOR235-1). Furthermore, early onset does not correlate with high abundance in adult. This study reveals a dynamic composition of the OSNs expressing different ORs in the developing olfactory epithelium.

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“…These mutants have defects in the development of the eyes, forebrain, and erythrocytes and die a few days before birth because of severe anemia (18). We analyzed mutant embryos at E16.5, when OSNs already express OR genes (11). The olfactory turbinates of Lhx2 Ϫ/Ϫ embryos appear to develop grossly normally, except for a slightly smaller size in comparison with wild-type embryos ( Fig.…”

Section: Lhx2mentioning

confidence: 99%

“…By targeted mutagenesis, all OSNs expressing the same OR were shown to project their axons to the same glomeruli in a remarkably precise manner, and these OR-specific projections to the olfactory bulb are influenced by the specificity of the expressed OR (9,10). The onset of OR expression occurs before the first contact between OSN axons and the forebrain in embryos, and OSNs express OR genes in the absence of the axonal target, the olfactory bulb (11).…”

mentioning

confidence: 99%

The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons

Hirota

Mombaerts

2004

Proc. Natl. Acad. Sci. U.S.A.

146

135

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In mice, Ϸ1,000 odorant receptor (OR) genes are expressed in olfactory sensory neurons (OSNs). Homeodomain sites can be recognized in the promoter and upstream regions of several OR genes. Here, using the yeast one-hybrid system and electrophoretic mobility shift assay, we report that Lhx2, a LIM-homeodomain protein, binds to the homeodomain site in the mouse M71 OR promoter region. In Lhx2-deficient mice, the morphology of the olfactory epithelium is grossly normal. However, expression of OMP is abolished and that of GAP43 is severely reduced, indicating that no mature and few immature OSNs are produced. M71 and other OR genes also are not expressed. OSN development appears to be arrested between the terminal differentiation into neurons and the transition to immature neurons. Thus, Lhx2 is required for complete development of OSNs in mice.I n the mammalian olfactory epithelium (OE), olfactory sensory neurons (OSNs) detect chemical stimuli in the external environment by expressing odorant receptor (OR) genes (1, 2). These genes encode proteins with a putative seven-transmembrane domain structure, a defining characteristic of G proteincoupled receptors. It is believed that an individual OSN expresses a single OR gene (3) from the Ϸ1,000 OR genes in the mouse genome (4), but the strength of the evidence for this one-neuron-one-receptor hypothesis has been questioned (5). An OR gene is expressed from a single allele in a given cell (6). The OE is thus a complex mosaic of Ϸ2,000 OSN populations, each defined as expressing one allele from a choice of 2 ϫ Ϸ1,000 genes. OSNs expressing the same OR gene typically reside within one of at least four zones in the OE (7,8), where they are interspersed with OSNs expressing other OR genes. By targeted mutagenesis, all OSNs expressing the same OR were shown to project their axons to the same glomeruli in a remarkably precise manner, and these OR-specific projections to the olfactory bulb are influenced by the specificity of the expressed OR (9, 10). The onset of OR expression occurs before the first contact between OSN axons and the forebrain in embryos, and OSNs express OR genes in the absence of the axonal target, the olfactory bulb (11).The mechanisms underlying OR gene choice and expression are not understood, but irreversible DNA rearrangements have been excluded (12, 13). Sequence analyses of human, mouse, and rat OR genes have revealed a variety of motifs upstream of the transcription start site, including O͞E-like, E-box, Ikaros, homeodomain, and methylation-sensitive vMYB motifs (14). However, an involvement in OR gene regulation has not been shown for any of these motifs. Short (9-kb) transgenes of two OR genes, MOR23 and M71, replicate most OR expression features (15). A region of 405 bp upstream of the MOR23 transcription start site is required for transgene expression. In this and other upstream OR regions, common sequence motifs of homeodomain and O͞E-like sites have been recognized (15).Here, we have conducted yeast one-hybrid screening (16) to identify transcr...

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Target-independent pattern specification in the olfactory epithelium

Cited by 143 publications

References 65 publications

The olfactory bulb as an independent developmental domain

The olfactory bulb as an independent developmental domain

Differential development of odorant receptor expression patterns in the olfactory epithelium: A quantitative analysis in the mouse septal organ

The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons

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