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

Lechner, Stefan; Frenzel, H; Wang, Rui; Lewin, Gary R.

doi:10.1038/emboj.2009.73

Cited by 84 publications

(104 citation statements)

References 64 publications

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“…At embryonic ages, action potential-firing neurons have very high input resistances, indicating that their expression of ion channels is very low. In other parts of the nervous system where embryonic neurons exhibit mature forms of electrical activity, an increase in the density of these currents also occurs during development (Bader et al, 1983;Krieger and Sears, 1988;Rothe et al, 1999;Lechner et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Early Emergence of Neural Activity in the Developing Mouse Enteric Nervous System

Hao¹,

Boesmans²,

Abbeel³

et al. 2011

J. Neurosci.

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Neurons of the enteric nervous system (ENS) arise from neural crest cells that migrate into and along the developing gastrointestinal tract. A subpopulation of these neural-crest derived cells express pan-neuronal markers early in development, shortly after they first enter the gut. However, it is unknown whether these early enteric "neurons" are electrically active. In this study we used live Ca 2ϩ imaging to examine the activity of enteric neurons from mice at embryonic day 11.5 (E11.5), E12.5, E15.5, and E18.5 that were dissociated and cultured overnight. PGP9.5-immunoreactive neurons from E11.5 gut cultures responded to electrical field stimulation with fast [Ca 2ϩ ] i transients that were sensitive to TTX and -conotoxin GVIA, suggesting roles for voltage-gated Na ϩ channels and N-type voltage-gated Ca 2ϩ channels. E11.5 neurons were also responsive to the nicotinic cholinergic agonist, dimethylphenylpiperazinium, and to ATP. In addition, spontaneous [Ca 2ϩ ] i transients were present. Similar responses were observed in neurons from older embryonic gut. Wholecell patch-clamp recordings performed on E12.5 enteric neurons after 2-10 h in culture revealed that these neurons fired both spontaneous and evoked action potentials. Together, our results show that enteric neurons exhibit mature forms of activity at early stages of ENS development. This is the first investigation to directly examine the presence of neural activity during enteric neuron development. Along with the spinal cord and hindbrain, the ENS appears to be one of the earliest parts of the nervous system to exhibit electrical activity.

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Section: Discussionmentioning

confidence: 99%

Early Emergence of Neural Activity in the Developing Mouse Enteric Nervous System

Hao¹,

Boesmans²,

Abbeel³

et al. 2011

J. Neurosci.

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“…Using whole-cell, patch-clamp techniques we directly recorded mechanosensitive currents in cultured sensory neurons [12][13][14][15][16][17][18][19][20] . We first asked whether co-culture of sensory neurons with different cellular components of the skin can modulate the activity of mechanosensitive currents.…”

Section: Keratinocyte Matrix Is Suppresses Mechanotransductionmentioning

confidence: 99%

“…1a) 20 . Practically all mechanoreceptors, classified by their very narrow action potential (AP) 13,15 , possess an RA-mechanosensitive current, as do many nociceptive neurons classified by their broad humped APs 13 . The proportion of sensory neurons with an RA-mechanosensitive current was ~44% of the recorded population (32/72 recorded cells on a laminin substrate, Fig.…”

Section: Keratinocyte Matrix Is Suppresses Mechanotransductionmentioning

confidence: 99%

Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons

et al. 2011

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2 These authors made an equal contribution. Basement membrane molecules such as laminin are important structural components of the skin 1-4 , but also serve as substrates for sensory neurons of the dorsal root ganglia (DRG) to grow in culture 5 . The main function of sensory neurons innervating the skin is to detect and relay relevant sensory stimuli, in particular mechanical stimuli 6 . It has long been known that sensory neurons with a nociceptive function (detecting potentially harmful stimuli) can have their endings in the epidermis 7-9 whereas mechanoreceptor endings (touch receptors) reside exclusively in the dermal layer [9][10] . Interestingly, the matrix environments of the epidermis and the dermis are very distinctive 11 . We showed that mechanosensitive currents required for touch receptor function depend on the presence of a protein tether which may function to couple mechanosensitive channels to a laminin-containing matrix 12 . The tether protein is not required for the mechanosensitivity of most nociceptive sensory neurons. Here we set out to address the idea that sensory mechanotransduction might be modulated by distinct matrix components made by different types of skin cells in different skin layers. We show that epidermal keratinocytes produce a matrix that is non-permissive for mechanotransduction and identify the factor responsible as laminin-332 (formerly known as laminin-5). Laminin matrices doped with small amounts of laminin-332 have a dramatically altered network structure that is non-permissive for tether attachment.We demonstrate a spatially restricted loss of mechanotransduction in neurite segments connected to laminin-332-containing matrices. Mutations in all three genes coding the trimeric laminin-332 protein complex can cause epidermolysis bullosa, a severe inherited skin blistering disease 1,3 . Human keratinocytes that produce a laminin-332 free matrix have no inhibitory activity on mechanotransduction. We have also discovered an activity of laminin-332 matrix in inhibiting sensory axon bifurcation. Our results reveal novel mechanisms whereby permissive and non-permissive substrates can spatially coordinate mechanotransduction in distinct domains within a single neuron. Results Keratinocyte matrix is suppresses mechanotransductionUsing whole-cell, patch-clamp techniques we directly recorded mechanosensitive currents in cultured sensory neurons [12][13][14][15][16][17][18][19][20] . We first asked whether co-culture of sensory neurons with different cellular components of the skin can modulate the activity of mechanosensitive currents. When sensory neurons are cultured on a laminin substrate, standardly-derived from Engelbreth-Holm-Swarm cells (EHS matrix, henceforth referred to as laminin), more than 90% of the cells exhibit a mechanosensitive current evoked using a small (~740 nm displacement) stimulus to the neurite 12, 14-15 . At least three types of mechanosensitive current can be measured in sensory neurons, classified according to their inactivation time constant τ 1 , rap...

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“…[11][12][13] Compared with nociceptors, mechanoreceptor mature faster. 14 The developmental mechanisms that generate the functional and anatomical diversity of sensory neurons are incompletely understood. Sensory neurons derive from neural crest cells that delaminate from the dorsal neural tube and migrate to condense into dorsal root ganglia.…”

Section: C-maf Controls Development and Function Of Cutaneous Mechanomentioning

confidence: 99%

The transcription factor c-Maf in sensory neuron development

2012

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

Cited by 84 publications

References 64 publications

Early Emergence of Neural Activity in the Developing Mouse Enteric Nervous System

Early Emergence of Neural Activity in the Developing Mouse Enteric Nervous System

Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons

The transcription factor c-Maf in sensory neuron development

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