ER stress transforms random olfactory receptor choice into axon targeting precision

Shayya, Hani J.; Kahiapo, Jerome K.; Duffié, Rachel; Lehmann, Katherine S.; Bashkirova, Lisa; Monahan, Kevin D.; Dalton, Ryan P.; Gao, Joanna; Song, Ji‐Hyun; Schieren, Ira; Belluscio, Leonardo; Lomvardas, Stavros

doi:10.1016/j.cell.2022.08.025

Cited by 25 publications

(21 citation statements)

References 88 publications

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“…Are these phenotypes a result of ORN apoptosis or other developmental events? If the former, is it due to the absence of neuronal activity or to improper receptor trafficking ( 20, 21 )? We show that all Or -expressing ORNs undergo massive apoptosis when Orco is absent.…”

Section: Introductionmentioning

confidence: 99%

Activity-dependent survival of odorant receptor neurons in ants

Sieriebriennikov,

Sieber,

Kolumba

et al. 2023

Preprint

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Olfaction is essential for complex social behavior in eusocial insects. To discriminate complex social cues, ants evolved an expanded number ofodorant receptor(Or) genes. Unlike most insect species, mutations in the obligate odorant co-receptor geneorcolead to loss of ∼80% antennal lobe glomeruli in ants. However, its cellular mechanism remains unclear. Here we demonstrate that this surprising neuronal phenotype results from massive apoptosis of odorant receptor neurons (ORNs) in the mid- to late-stages of pupal development. Further bulk and single-nucleus transcriptome analysis show that, although the majority oforco-expressing ORNs die inorcomutants, a small proportion of them survive: they expressionotropic receptor(Ir) genes that form IR complexes. In addition, we found that someOrgenes are expressed in mechanosensory neurons as well as non-neuronal cells, possibly due to the leaky regulation from nearby non-Orgenes. Our findings suggest that chemosensory receptors are required for activity-dependent survival of developing ORNs in ants.

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Section: Introductionmentioning

confidence: 99%

Activity-dependent survival of odorant receptor neurons in ants

Sieriebriennikov,

Sieber,

Kolumba

et al. 2023

Preprint

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“…These include odorant-invoked neuronal activity, and the intrinsic G protein signaling activity of the OR protein (Connelly et al, 2013;Nakashima et al, 2013Nakashima et al, , 2019Serizawa et al, 2003Serizawa et al, , 2006. However, recent work has demonstrated a direct role for the amino acid sequence of the selected OR in regulating gene expression (Shayya et al, 2022). When a ribosome translates the OR coding sequence into a protein, it leads to the activation of the unfolded protein response (UPR).…”

Section: Monogenic and Monoallelic Expression Of Orsmentioning

confidence: 99%

“…Accordingly, for each OSN, the expression levels of non‐OR genes can be used to predict the identity of the expressed OR with a high degree of accuracy. Critically, the OR‐correlated genes include many axon guidance molecules which, together with zonal expression of additional axon guidance molecules (Mori & Sakano, 2011; Takeuchi et al, 2010), accomplishes the targeting of OSN axons to specific glomeruli in the olfactory bulb (Greer et al, 2016; Mombaerts et al, 1996; Nakashima et al, 2019; Shayya et al, 2022; Shykind et al, 2004; I.‐H. Wang et al, 2022).…”

Section: Monogenic and Monoallelic Expression Of Orsmentioning

confidence: 99%

Epigenetic programming of stochastic olfactory receptor choice

Yusuf,

Monahan

2024

Genesis

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SummaryThe mammalian sense of smell relies upon a vast array of receptor proteins to detect odorant compounds present in the environment. The proper deployment of these receptor proteins in olfactory sensory neurons is orchestrated by a suite of epigenetic processes that remodel the olfactory genes in differentiating neuronal progenitors. The goal of this review is to elucidate the central role of gene regulatory processes acting in neuronal progenitors of olfactory sensory neurons that lead to a singular expression of an odorant receptor in mature olfactory sensory neurons. We begin by describing the principal features of odorant receptor gene expression in mature olfactory sensory neurons. Next, we delineate our current understanding of how these features emerge from multiple gene regulatory mechanisms acting in neuronal progenitors. Finally, we close by discussing the key gaps in our understanding of how these regulatory mechanisms work and how they interact with each other over the course of differentiation.

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“…The formation of the glomerular map in the OB relies on several families of axon guidance molecules and cell adhesion molecules (CAMs) whose expression and function can be modulated by neuronal activity. Coarse targeting of ORN axons along the three‐dimensional planes of the OB is modulated by the differential expression of axon guidance receptors in ORNs, such as Neuropilin1 and Robo2, which in certain cases can be modulated by neuronal activity (Cho et al, 2007; Cho et al, 2012; Cutforth et al, 2003; Imai et al, 2006; Imai & Sakano, 2009; Mori & Sakano, 2011; Nakashima et al, 2013; Shayya et al, 2022; Takeuchi et al, 2010). The coarse targeting of ORN axons is then refined through the coalescence of axons expressing the same OR into specific glomeruli.…”

Section: Introductionmentioning

confidence: 99%

Insertion of a neomycin selection cassette in the Amigo1 locus alters gene expression in the olfactory epithelium leading to region‐specific defects in olfactory receptor neuron development

Raja,

Dumontier,

Phen

et al. 2024

Genesis

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SummaryDuring development of the nervous system, neurons connect to one another in a precisely organized manner. Sensory systems provide a good example of this organization, whereby the composition of the outside world is represented in the brain by neuronal maps. Establishing correct patterns of neural circuitry is crucial, as inaccurate map formation can lead to severe disruptions in sensory processing. In rodents, olfactory stimuli modulate a wide variety of behaviors essential for survival. The formation of the olfactory glomerular map is dependent on molecular cues that guide olfactory receptor neuron axons to broad regions of the olfactory bulb and on cell adhesion molecules that promote axonal sorting into specific synaptic units in this structure. Here, we demonstrate that the cell adhesion molecule Amigo1 is expressed in a subpopulation of olfactory receptor neurons, and we investigate its role in the precise targeting of olfactory receptor neuron axons to the olfactory bulb using a genetic loss‐of‐function approach in mice. While ablation of Amigo1 did not lead to alterations in olfactory sensory neuron axonal targeting, our experiments revealed that the presence of a neomycin resistance selection cassette in the Amigo1 locus can lead to off‐target effects that are not due to loss of Amigo1 expression, including unexpected altered gene expression in olfactory receptor neurons and reduced glomerular size in the ventral region of the olfactory bulb. Our results demonstrate that insertion of a neomycin selection cassette into the mouse genome can have specific deleterious effects on the development of the olfactory system and highlight the importance of removing antibiotic resistance cassettes from genetic loss‐of‐function mouse models when studying olfactory system development.

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ER stress transforms random olfactory receptor choice into axon targeting precision

Cited by 25 publications

References 88 publications

Activity-dependent survival of odorant receptor neurons in ants

Activity-dependent survival of odorant receptor neurons in ants

Epigenetic programming of stochastic olfactory receptor choice

Insertion of a neomycin selection cassette in the Amigo1 locus alters gene expression in the olfactory epithelium leading to region‐specific defects in olfactory receptor neuron development

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