Olfactory sensory axon growth and branching is influenced by sonic hedgehog

Gong, Qizhi; Chen, Huaiyang; Farbman, Albert I.

doi:10.1002/dvdy.22005

Cited by 19 publications

(16 citation statements)

References 54 publications

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“…In light of the OR transport regulatory mechanism identified in flies, it is interesting to note that the most extensively studied mammalian Hh family member, Sonic hedgehog (Shh), is present in human nasal mucus as well as in dendrites of OSN target neurons in the rat olfactory bulb of the brain (8)(9)(10). The localization in target neurons is in line with the findings that Shh influences OSN axon growth and branching (11).…”

mentioning

confidence: 56%

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

Maurya

Bohm

Alenius

2017

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

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The ciliary localization of odorant receptors (ORs) is evolutionary conserved and essential for olfactory transduction. However, how the transport of ORs is regulated in mammalian olfactory sensory neurons is poorly understood. Here we demonstrate that odorant responsiveness and OR transport is regulated by the Hedgehog pathway. OR transport is inhibited by conditional gene inactivation of the Hedgehog signal mediator Smoothened (Smo) as well as by systemic administration of the Smo inhibitor vismodegib, a clinically used anticancer drug reported to distort smell perception in patients. The ciliary phenotype of Smo inhibition is haploinsufficient, cell autonomous, and correlates with the accumulation of OR-containing putative transport vesicles in the cytosol. The Smo-dependent OR transport route works in parallel with a low basal transport of vesicle containing both ORs and other olfactory transduction components. These findings both define a physiological function of Hedgehog signaling in olfaction and provide an important evolutionary link between olfaction and the requirement of a ciliary compartment for Hedgehog signaling.

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confidence: 56%

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

Maurya

Bohm

Alenius

2017

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

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“…It is also possible that OR gene expression is determined by intrinsic genomic factors [35,36] and that differential odour exposure during their continued development affects their survival as the OSN axons grow from the epithelium to the glomerulus [37]. Another possibility is that activation through odour exposure modulates branching of the axon terminals once they reach the glomerulus [38]. Activation could also enhance dendritic arborizations of mitral cells in the glomerulus [39].…”

Section: Resultsmentioning

confidence: 99%

Effects of in utero odorant exposure on neuroanatomical development of the olfactory bulb and odour preferences

2010

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Human babies and other young mammals prefer food odours and flavours of their mother's diet during pregnancy as well as their mother's individually distinctive odour. Newborn mice also prefer the individual odours of more closely related-even unfamiliar-lactating females. If exposure to in utero odorantswhich include metabolites from the mother's diet and the foetus's genetically determined individual odour-helps shape the neuroanatomical development of the olfactory bulb, this could influence the perception of such biologically important odours that are preferred after birth. We exposed gene-targeted mice during gestation and nursing to odorants that activate GFP-tagged olfactory receptors (ORs) and then measured the effects on the size of tagged glomeruli in the olfactory bulb where axons from olfactory sensory neurons (OSNs) coalesce by OR type. We found significantly larger tagged glomeruli in mice exposed to these activating odorants in amniotic fluid, and later in mother's milk, as well as significant preferences for the activating odour. Larger glomeruli comprising OSNs that respond to consistently encountered odorants should enhance detection and discrimination of these subsequently preferred odours, which in nature would facilitate selection of palatable foods and kin recognition, through similarities in individual odours of relatives.

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“…The presence of Ptch and Smo in newly generated migrating neurons and the location of Ptch and Smo in the growth cones of these neurons (Figs. 2, 3) suggest that Shh signaling could contribute to or control the growth of these neurons, much like Shh’s role in axonal growth of other types of neurons (Trousse et al, 2001; Charron et al, 2003; Gong et al, 2009; Hammond et al, 2009; Chou et al, 2010; Parra and Zou, 2010). However, whether Shh signaling regulates axonal or dendritic growth, where and how Shh is produced, and the underlying mechanisms involved, will all require further study.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to acting as a mitogen for cells with stem-cell-like properties, Shh also promotes the growth of axons of young neurons soon after they are generated from progenitor cells. This aspect of Shh in axonal growth has been demonstrated in several types of neurons, including spinal cord commissural neurons (Charron et al, 2003; Parra and Zou, 2010), retinal ganglion cells (Trousse et al, 2001), olfactory sensory neurons (Gong et al, 2009; Chou et al, 2010), and midbrain dopaminergic neurons (Hammond et al, 2009). However, whether Shh signaling plays roles in the development of the postmitotic neurons in the hippocampus is not known.…”

mentioning

confidence: 95%

Subcellular localization of patched and smoothened, the receptors for sonic hedgehog signaling, in the hippocampal neuron

Petralia

Schwartz

Wang

et al. 2011

J of Comparative Neurology

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Cumulative evidence suggests that, aside from patterning the embryonic neural tube, Sonic hedgehog (Shh) signaling plays important roles in the mature nervous system. In this study, we investigate the expression and localization of the Shh signaling receptors, Patched (Ptch) and Smoothened (Smo), in the hippocampal neurons of young and mature rats. Reverse transcriptase-polymerase chain reaction and immunoblotting analyses show that the expression of Ptch and Smo remains at a moderate level in young postnatal and adult brains. By using immunofluorescence light microscopy and immunoelectron microscopy, we examine the spatial distribution of Ptch and Smo within the hippocampal neurons. In young developing neurons, Ptch and Smo are present in the processes and are clustered at their growth cones. In mature neurons, Ptch and Smo are concentrated in dendrites, spines, and postsynaptic sites. Synaptic Ptch and Smo often co-exist with unusual structures—synaptic spinules and autophagosomes. Our results reveal the anatomical organization of the Shh receptors within both the young and the mature hippocampal neurons.

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Olfactory sensory axon growth and branching is influenced by sonic hedgehog

Cited by 19 publications

References 54 publications

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

Hedgehog signaling regulates ciliary localization of mouse odorant receptors

Effects of in utero odorant exposure on neuroanatomical development of the olfactory bulb and odour preferences

Subcellular localization of patched and smoothened, the receptors for sonic hedgehog signaling, in the hippocampal neuron

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