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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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Three waves of mechanosensitivity acquisition. The proportion of neurons that acquire mechanosensitivity in each of the three waves is calculated after correcting for cell size sampling (see Materials and methods). For each of the three waves, the key characteristics of the neurons that acquire mechanosensitivity is indicated (text boxes).
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f4: Three waves of mechanosensitivity acquisition. The proportion of neurons that acquire mechanosensitivity in each of the three waves is calculated after correcting for cell size sampling (see Materials and methods). For each of the three waves, the key characteristics of the neurons that acquire mechanosensitivity is indicated (text boxes).

Mentions: The proportion of cells with a mechanosensitive current (shown in Figure 2B) was calculated from the recorded population. However, the cell size distribution of the recorded cells, especially at early stages, was not identical to that of the total population measured morphologically. Therefore, a weighted analysis was made to estimate the true proportion of cells with mechanosensitive currents in cultures from different embryonic stages (Figure 4), for a detailed description of the calculation see Supplementary Figure S2). This analysis shows more quantitatively the three waves of mechanosensitive current acquisition in the different neuronal populations. First, very early differentiating neurons already present at E13.5 with large cell bodies characteristic of mechanoreceptors acquire an RA-current, this population stays relatively constant at approximately 15% of the total through to birth. In fact, at every developmental stage after E13.5 virtually all neurons with a narrow AP possess an RA-type current (76.5% at E13.5 to 87.5% at E18.5). Second, a later differentiating wave consisting of nociceptors with a humped AP acquire an RA-current in large numbers at E15.5, and this population makes up around 50% of all cells by E18.5. However, not all nociceptive neurons have acquired mechanosensitivity by birth. Only after birth do a substantial number of the remaining nociceptors acquire an SA-current (Figure 4). The SA-current is pharmacologically and biophysically distinct from the RA-type current, and at birth, the distribution of mechanosensitive currents in mechanoreceptors and nociceptors largely reflects that observed in the adult (Hu and Lewin, 2006).


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

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

Three waves of mechanosensitivity acquisition. The proportion of neurons that acquire mechanosensitivity in each of the three waves is calculated after correcting for cell size sampling (see Materials and methods). For each of the three waves, the key characteristics of the neurons that acquire mechanosensitivity is indicated (text boxes).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Three waves of mechanosensitivity acquisition. The proportion of neurons that acquire mechanosensitivity in each of the three waves is calculated after correcting for cell size sampling (see Materials and methods). For each of the three waves, the key characteristics of the neurons that acquire mechanosensitivity is indicated (text boxes).
Mentions: The proportion of cells with a mechanosensitive current (shown in Figure 2B) was calculated from the recorded population. However, the cell size distribution of the recorded cells, especially at early stages, was not identical to that of the total population measured morphologically. Therefore, a weighted analysis was made to estimate the true proportion of cells with mechanosensitive currents in cultures from different embryonic stages (Figure 4), for a detailed description of the calculation see Supplementary Figure S2). This analysis shows more quantitatively the three waves of mechanosensitive current acquisition in the different neuronal populations. First, very early differentiating neurons already present at E13.5 with large cell bodies characteristic of mechanoreceptors acquire an RA-current, this population stays relatively constant at approximately 15% of the total through to birth. In fact, at every developmental stage after E13.5 virtually all neurons with a narrow AP possess an RA-type current (76.5% at E13.5 to 87.5% at E18.5). Second, a later differentiating wave consisting of nociceptors with a humped AP acquire an RA-current in large numbers at E15.5, and this population makes up around 50% of all cells by E18.5. However, not all nociceptive neurons have acquired mechanosensitivity by birth. Only after birth do a substantial number of the remaining nociceptors acquire an SA-current (Figure 4). The SA-current is pharmacologically and biophysically distinct from the RA-type current, and at birth, the distribution of mechanosensitive currents in mechanoreceptors and nociceptors largely reflects that observed in the adult (Hu and Lewin, 2006).

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