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Developmental waves of mechanosensitivity acquisition in sensory neuron subtypes during embryonic development.

Lechner SG, Frenzel H, Wang R, Lewin GR - EMBO J. (2009)

Bottom Line: Sensory neurons that are mechanoreceptors or proprioceptors acquire mature mechanotransduction indistinguishable from the adult already at E13.In contrast, most nociceptive (pain sensing) sensory neurons acquire mechanosensitive competence as a result of exposure to target-derived nerve growth factor.The highly regulated process of mechanosensory acquisition unveiled here, reveals new strategies to identify molecules required for sensory neuron mechanotransduction.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.

ABSTRACT
Somatic sensation relies on the transduction of physical stimuli into electrical signals by sensory neurons of the dorsal root ganglia. Little is known about how and when during development different types of sensory neurons acquire transduction competence. We directly investigated the emergence of electrical excitability and mechanosensitivity of embryonic and postnatal mouse sensory neurons. We show that sensory neurons acquire mechanotransduction competence coincident with peripheral target innervation. Mechanotransduction competence arises in different sensory lineages in waves, coordinated by distinct developmental mechanisms. Sensory neurons that are mechanoreceptors or proprioceptors acquire mature mechanotransduction indistinguishable from the adult already at E13. This process is independent of neurotrophin-3 and may be driven by a genetic program. In contrast, most nociceptive (pain sensing) sensory neurons acquire mechanosensitive competence as a result of exposure to target-derived nerve growth factor. The highly regulated process of mechanosensory acquisition unveiled here, reveals new strategies to identify molecules required for sensory neuron mechanotransduction.

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Related in: MedlinePlus

(A) Example traces showing the RA- and IA-currents with different mechanical stimuli in the same cell. Neurons with an IA-current in response to the standard stimulus (sustained, left trace, τ=11.9±3.4 ms, n=9) exhibit an RA-type current (τ=1.2±0.3 ms, n=9) with rapid poking stimuli. (B) Stacked histograms showing the proportions of P0–P1 neurons with different mechanically gated currents cultured for 24 h in the absence (control) and in the presence of NGF, respectively.
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f7: (A) Example traces showing the RA- and IA-currents with different mechanical stimuli in the same cell. Neurons with an IA-current in response to the standard stimulus (sustained, left trace, τ=11.9±3.4 ms, n=9) exhibit an RA-type current (τ=1.2±0.3 ms, n=9) with rapid poking stimuli. (B) Stacked histograms showing the proportions of P0–P1 neurons with different mechanically gated currents cultured for 24 h in the absence (control) and in the presence of NGF, respectively.

Mentions: The IA-mechanosensitive current was found in nearly half of the neurons in NGF-treated cultures, but this current is found rarely in the adult DRG (Hu and Lewin, 2006) and was also rare in embryonic sensory neurons cultured for a few hours (Figure 2B). All cells with an IA-current could also be shown to possess an RA-current, thus a rapid prodding stimulus invariably evoked an RA-current that was kinetically indistinguishable from the RA-currents in other cells (Figure 7A) (McCarter and Levine, 2006). Our data suggested that NGF can induce an IA-current in embryonic sensory neurons. This effect was seemingly independent of developmental stage as incubation of postnatal sensory neurons with NGF for 24 h also increased the proportion of neurons with an IA-current (Figure 7B). Taken together, our data suggest that target-derived NGF is an inductive factor for mechanosensitive currents. Consistent with this idea, we find that exposure of neurons to NGF before target innervation is sufficient to prematurely induce mechanosensitive currents in nociceptive sensory neurons.


Developmental waves of mechanosensitivity acquisition in sensory neuron subtypes during embryonic development.

Lechner SG, Frenzel H, Wang R, Lewin GR - EMBO J. (2009)

(A) Example traces showing the RA- and IA-currents with different mechanical stimuli in the same cell. Neurons with an IA-current in response to the standard stimulus (sustained, left trace, τ=11.9±3.4 ms, n=9) exhibit an RA-type current (τ=1.2±0.3 ms, n=9) with rapid poking stimuli. (B) Stacked histograms showing the proportions of P0–P1 neurons with different mechanically gated currents cultured for 24 h in the absence (control) and in the presence of NGF, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2664657&req=5

f7: (A) Example traces showing the RA- and IA-currents with different mechanical stimuli in the same cell. Neurons with an IA-current in response to the standard stimulus (sustained, left trace, τ=11.9±3.4 ms, n=9) exhibit an RA-type current (τ=1.2±0.3 ms, n=9) with rapid poking stimuli. (B) Stacked histograms showing the proportions of P0–P1 neurons with different mechanically gated currents cultured for 24 h in the absence (control) and in the presence of NGF, respectively.
Mentions: The IA-mechanosensitive current was found in nearly half of the neurons in NGF-treated cultures, but this current is found rarely in the adult DRG (Hu and Lewin, 2006) and was also rare in embryonic sensory neurons cultured for a few hours (Figure 2B). All cells with an IA-current could also be shown to possess an RA-current, thus a rapid prodding stimulus invariably evoked an RA-current that was kinetically indistinguishable from the RA-currents in other cells (Figure 7A) (McCarter and Levine, 2006). Our data suggested that NGF can induce an IA-current in embryonic sensory neurons. This effect was seemingly independent of developmental stage as incubation of postnatal sensory neurons with NGF for 24 h also increased the proportion of neurons with an IA-current (Figure 7B). Taken together, our data suggest that target-derived NGF is an inductive factor for mechanosensitive currents. Consistent with this idea, we find that exposure of neurons to NGF before target innervation is sufficient to prematurely induce mechanosensitive currents in nociceptive sensory neurons.

Bottom Line: Sensory neurons that are mechanoreceptors or proprioceptors acquire mature mechanotransduction indistinguishable from the adult already at E13.In contrast, most nociceptive (pain sensing) sensory neurons acquire mechanosensitive competence as a result of exposure to target-derived nerve growth factor.The highly regulated process of mechanosensory acquisition unveiled here, reveals new strategies to identify molecules required for sensory neuron mechanotransduction.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.

ABSTRACT
Somatic sensation relies on the transduction of physical stimuli into electrical signals by sensory neurons of the dorsal root ganglia. Little is known about how and when during development different types of sensory neurons acquire transduction competence. We directly investigated the emergence of electrical excitability and mechanosensitivity of embryonic and postnatal mouse sensory neurons. We show that sensory neurons acquire mechanotransduction competence coincident with peripheral target innervation. Mechanotransduction competence arises in different sensory lineages in waves, coordinated by distinct developmental mechanisms. Sensory neurons that are mechanoreceptors or proprioceptors acquire mature mechanotransduction indistinguishable from the adult already at E13. This process is independent of neurotrophin-3 and may be driven by a genetic program. In contrast, most nociceptive (pain sensing) sensory neurons acquire mechanosensitive competence as a result of exposure to target-derived nerve growth factor. The highly regulated process of mechanosensory acquisition unveiled here, reveals new strategies to identify molecules required for sensory neuron mechanotransduction.

Show MeSH
Related in: MedlinePlus