Neuronal regeneration: Lessons from the olfactory system

Murray, Richard C.; Calof, Anne L.

doi:10.1006/scdb.1999.0329

Cited by 47 publications

(42 citation statements)

References 89 publications

(122 reference statements)

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“…Alternatively, differentiated neurons may produce an inhibitory signal that prevents progenitor cells from dividing and generating new neurons as long as the normal compliment of neurons is intact. Several studies support the former hypothesis by demonstrating an increase in progenitor cell proliferation after injury (for review, see Murray and Calof, 1999). No studies, however, have been able to rule out the latter mechanism completely.…”

Section: Receptor Turnover In Other Sensory Systemsmentioning

confidence: 98%

Inhibition of Caspases Prevents Ototoxic and Ongoing Hair Cell Death

2002

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Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment.Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dosedependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.

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Section: Receptor Turnover In Other Sensory Systemsmentioning

confidence: 98%

Inhibition of Caspases Prevents Ototoxic and Ongoing Hair Cell Death

2002

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“…The patterning and differentiation of placodes appears to be the result of complex epithelial-mesenchymal interactions, often involving secreted factors such as Wnts, bone morphogenetic proteins (BMPs) and sonic hedgehog (SHH) (Jiang et al, 1999;Jung et al, 1998;Mikkola and Millar, 2006;Plikus et al, 2008). Many placode-derived tissues also regenerate, making them ideal for investigating epithelial stem cells and their niches (Blanpain et al, 2007;Kawauchi et al, 2004;Murray and Calof, 1999;Plikus et al, 2008;Watt et al, 2006). In mammals, placode-derived sensory systems provide some of the few examples of robust neuronal regeneration following injury (Murray and Calof, 1999); the tongue, for example, readily regenerates its sensory (gustatory) cells following damage or denervation (Beidler and Smallman, 1965;Cheal and Oakley, 1977).…”

Section: Introductionmentioning

confidence: 99%

Follistatin modulates a BMP autoregulatory loop to control the size and patterning of sensory domains in the developing tongue

et al. 2009

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The regenerative capacity of many placode-derived epithelial structures makes them of interest for understanding the molecular control of epithelial stem cells and their niches. Here, we investigate the interaction between the developing epithelium and its surrounding mesenchyme in one such system, the taste papillae and sensory taste buds of the mouse tongue. We identify follistatin (FST) as a mesenchymal factor that controls size, patterning and gustatory cell differentiation in developing taste papillae. FST limits expansion and differentiation of Sox2-expressing taste progenitor cells and negatively regulates the development of taste papillae in the lingual epithelium: in Fst -/-tongue, there is both ectopic development of Sox2-expressing taste progenitors and accelerated differentiation of gustatory cells. Loss of Fst leads to elevated activity and increased expression of epithelial Bmp7; the latter effect is consistent with BMP7 positive autoregulation, a phenomenon we demonstrate directly. We show that FST and BMP7 influence the activity and expression of other signaling systems that play important roles in the development of taste papillae and taste buds. In addition, using computational modeling, we show how aberrations in taste papillae patterning in Fst -/-mice could result from disruption of an FST-BMP7 regulatory circuit that normally suppresses noise in a process based on diffusion-driven instability. Because inactivation of Bmp7 rescues many of the defects observed in Fst -/-tongue, we conclude that interactions between mesenchyme-derived FST and epithelial BMP7 play a central role in the morphogenesis, innervation and maintenance of taste buds and their stem/progenitor cells.

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“…Unlike other neural regions, neurogenesis proceeds throughout life in OE, allowing studies of stem cell behavior to be conducted in the regenerating adult nervous system, as well as during development [1]. Studies of mouse OE have shown that olfactory receptor neurons (ORNs) are products of a lineage that contains distinct proliferating cell types ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Identification and molecular regulation of neural stem cells in the olfactory epithelium

Beites

Kawauchi

Crocker

et al. 2005

Experimental Cell Research

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The sensory neurons that subserve olfaction, olfactory receptor neurons (ORNs), are regenerated throughout life, making the neuroepithelium in which they reside [the olfactory epithelium (OE)] an excellent model for studying how intrinsic and extrinsic factors regulate stem cell dynamics and neurogenesis during development and regeneration. Numerous studies indicate that transcription factors and signaling molecules together regulate generation of ORNs from stem and progenitor cells during development, and work on regenerative neurogenesis indicates that these same factors may operate at postnatal ages as well. This review describes our current knowledge of the identity of the OE neural stem cell; the different cell types that are thought to be the progeny (directly or indirectly) of this stem cell; and the factors that influence cell differentiation in the OE neuronal lineage. We review data suggesting that (1) the ORN lineage contains three distinct proliferating cell types-a stem cell and two populations of transit amplifying cells; (2) in established OE, these three cell types are present within the basal cell compartment of the epithelium; and (3) the stem cell that gives rise ultimately to ORNs may also generate two glial cell types of the primary olfactory pathway: sustentacular cells (SUS), which lie within OE proper; and olfactory ensheathing cells (OEC), which envelope the olfactory nerve. In addition, we describe factors that are both made by and found within the microenvironment of OE stem and progenitor cells, and which exert crucial growth regulatory effects on these cells. Thus, as with other regenerating tissues, the basis of regeneration in the OE appears be a population of stem cells, which resides within a microenvironment (niche) consisting of factors crucial for maintenance of its capacity for proliferation and differentiation. D

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Neuronal regeneration: Lessons from the olfactory system

Cited by 47 publications

References 89 publications

Inhibition of Caspases Prevents Ototoxic and Ongoing Hair Cell Death

Inhibition of Caspases Prevents Ototoxic and Ongoing Hair Cell Death

Follistatin modulates a BMP autoregulatory loop to control the size and patterning of sensory domains in the developing tongue

Identification and molecular regulation of neural stem cells in the olfactory epithelium

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