Emergence of functional sensory subtypes as defined by transient receptor potential channel expression

The existence of heterogeneous populations of dorsal root ganglion (DRG) neurons conveying different somatosensory information is the basis for the perception of touch, temperature, and pain. A differential expression of transient receptor potential (TRP) cation channels contributes to this functional heterogeneity. However, little is known about the development of functionally diverse neuronal subpopulations. Here, we use calcium imaging of acutely dissociated mouse sensory neurons and quantitative reverse transcription PCR to show that TRP cation channels emerge in waves, with the diversification of functional groups starting at embryonic day 12.5 (E12.5) and extending well into the postnatal life. Functional responses of voltage-gated calcium channels were present in DRG neurons at E11.5 and reached adult levels by E14.5. Responses to capsaicin, menthol, and cinnamaldehyde were first seen at E12.5, E16.5, and postnatal day 0 (P0), when the mRNA for TRP cation channel, subfamily V, member 1 (TRPV1), TRP cation channel, subfamily M, member 8 (TRPM8), and TRP cation channel, subfamily A, member 1 (TRPA1), respectively, was first detected. Cold-sensitive neurons were present before the expression or functional responses of TRPM8 or TRPA1. Our data support a lineage relationship in which TRPM8- and TRPA1-expressing sensory neurons derive from the population of TRPV1-expressing neurons. The TRPA1 subpopulation of neurons emerges independently in two distinct classes of nociceptors: around birth in the peptidergic population and after P14 in the nonpeptidergic class. This indicates that neurons with similar receptive properties can be generated in different sublineages at different developmental stages. This study describes for the first time the emergence of functional subtypes of sensory neurons, providing new insight into the development of nociception and thermoreception

A Local Action of Neurotrophin-3 Prevents the Death of Proliferating Sensory Neuron Precursor Cells

AbstractThe role of neurotrophin-3 (NT-3) in early development of the dorsal root ganglion was investigated. Excessive cell death in the dorsal root ganglion of mice that carry a deleted NT-3 gene (NT-3−/− mice) preceded the period of programmed cell death, detected by the TUNEL method, and caused a reduction in the number of proliferating precursors without altering the proportion of proliferating cells to total number of neurons. Furthermore, the majority of proliferating cells detected by bromodeoxyuridine incorporation also stained with the TUNEL method. NT-3 mRNA was expressed locally in the embryonic, but not the postnatal dorsal root ganglion. Most cultured early embryonic NT-3−/− neurons died in the absence of exogenous NT-3 as did the wild-type neurons when cultured with NT-3 neutralizing antibodies, suggesting that NT-3 acts locally to prevent the death of proliferating sensory precursor cells during neurogenesis. Thus, NT-3 may inflict constraints on the number of proliferating precursor cells and thereby affect the number of neurons generated during development of the peripheral nervous system

The boundary cap: a source of neural crest stem cells that generate multiple sensory neuron subtypes

The boundary cap (BC) is a transient neural crest-derived group of cells located at the dorsal root entry zone (DREZ) that have been shown to differentiate into sensory neurons and glia in vivo. We find that when placed in culture, BC cells self-renew, show multipotency in clonal cultures and express neural crest stem cell (NCSCs) markers. Unlike sciatic nerve NCSCs, the BC-NCSC (bNCSCs) generates sensory neurons upon differentiation. The bNCSCs constitute a common source of cells for functionally diverse types of neurons, as a single bNCSC can give rise to several types of nociceptive and thermoreceptive sensory neurons. Our data suggests that BC cells comprise a source of multipotent sensory specified stem cells that persist throughout embryogenesis

The effect of cattle slurry in combination with nitrate and the nitrification inhibitor dicyandiamide on in situ nitrous oxide and dinitrogen emissions

peer-reviewedA field study was conducted to determine the effect of the nitrification inhibitor dicyandiamide (DCD) on N2O and N2 emissions after cattle slurry (CS) application in the presence of nitrate (NO3) fertiliser on seven different occasions (between March 2009 and March 2011). N2O emissions from CS in the presence of NO3 fertiliser were very high (0.4–8.7% of applied N) over a 20-day period, under mild moist conditions. Emissions were significantly larger from the CS treatment compared to an NH4+-N source, supplying the same rate of N as in the slurry. This study supports the view that organic fertilisers should not be applied at the same time as nitrate-based fertilisers, as significant increases in N2O emissions occur. The average N2O mole fraction (N2O/(N2O + N2)) over all seven application dates was 0.34 for CSNO3 compared to 0.24 for the NH4ClNO3 treatment, indicating the dominance of N2 emissions. The rate of nitrification in CSNO3 was slower than in NH4ClNO3, and DCD was found to be an effective nitrification inhibitor in both treatments. However, as N2O emissions were found to be predominantly associated with the NO3 pool, the effect of DCD in lowering N2O emissions is limited in the presence of a NO3 fertiliser. To obtain the maximum cost-benefit of DCD in lowering N2O emissions, under mild moist conditions, it should not be applied to a nitrate containing fertiliser (e.g. ammonium nitrate or calcium ammonium nitrate), and therefore the application of DCD should be restricted to ammonium-based organic or synthetic fertilisers.This research was funded by the Irish National Development Plan, through the Research Stimulus Fund (RSF 07 519), administered by the Irish Department of Agriculture, Food and the Marine

Lingual deficits in neurotrophin double knockout mice

Brain-derived neurotrophic factor (BDNF) and Neurotrophin 3 (NT-3) are members of the neurotrophin family and are expressed in the developing and adult tongue papillae. BDNF null-mutated mice exhibit specific impairments related to innervation and development of the gustatory system while NT-3 null mice have deficits in their lingual somatosensory innervation. To further evaluate the functional specificity of these neurotrophins in the peripheral gustatory system, we generated double BDNF/NT-3 knockout mice and compared the phenotype to BDNF −/− and wild-type mice. Taste papillae morphology was severely distorted in BDNF −/− x NT-3 −/− mice compared to single BDNF −/− and wild-type mice. The deficits were found throughout the tongue and all gustatory papillae. There was a significant loss of fungiform papillae and the papillae were smaller in size compared to BDNF −/− and wild-type mice. Circumvallate papillae in the double knockouts were smaller and did not contain any intraepithelial nerve fibers. BDNF −/− x NT-3 −/− mice exhibited additive losses in both somatosensory and gustatory innervation indicating that BDNF and NT-3 exert specific roles in the innervation of the tongue. However, the additional loss of fungiform papillae and taste buds in BDNF −/− x NT-3 −/− mice compared to single BDNF knockout mice indicate a synergistic functional role for both BDNF-dependent gustatory and NT-3-dependent somatosensory innervations in taste bud and taste papillae innervation and development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47465/1/11068_2005_Article_3330.pd

Challenges of accounting nitrous oxide emissions from agricultural crop residues

Crop residues are important inputs of carbon (C) and nitrogen (N) to soils and thus directly and indirectly affect nitrous oxide (N$_2$O) emissions. As the current inventory methodology considers N inputs by crop residues as the sole determining factor for N$_2$O emissions, it fails to consider other underlying factors and processes. There is compelling evidence that emissions vary greatly between residues with different biochemical and physical characteristics, with the concentrations of mineralizable N and decomposable C in the residue biomass both enhancing the soil N$_2$O production potential. High concentrations of these components are associated with immature residues (e.g., cover crops, grass, legumes, and vegetables) as opposed to mature residues (e.g., straw). A more accurate estimation of the short-term (months) effects of the crop residues on N$_2$O could involve distinguishing mature and immature crop residues with distinctly different emission factors. The medium-term (years) and long-term (decades) effects relate to the effects of residue management on soil N fertility and soil physical and chemical properties, considering that these are affected by local climatic and soil conditions as well as land use and management. More targeted mitigation efforts for N$_2$O emissions, after addition of crop residues to the soil, are urgently needed and require an improved methodology for emission accounting. This work needs to be underpinned by research to (1) develop and validate N$_2$O emission factors for mature and immature crop residues, (2) assess emissions from belowground residues of terminated crops, (3) improve activity data on management of different residue types, in particular immature residues, and (4) evaluate long-term effects of residue addition on N$_2$O emissions

Challenges of accounting nitrous oxide emissions from agricultural crop residues

Crop residues are important inputs of carbon (C) and nitrogen (N) to soils and thus directly and indirectly affect nitrous oxide (N2O) emissions. As the current inventory methodology considers N inputs by crop residues as the sole determining factor for N2O emissions, it fails to consider other underlying factors and processes. There is compelling evidence that emissions vary greatly between residues with different biochemical and physical characteristics, with the concentrations of mineralizable N and decomposable C in the residue biomass both enhancing the soil N2O production potential. High concentrations of these components are associated with immature residues (e.g., cover crops, grass, legumes, and vegetables) as opposed to mature residues (e.g., straw). A more accurate estimation of the short-term (months) effects of the crop residues on N2O could involve distinguishing mature and immature crop residues with distinctly different emission factors. The medium-term (years) and long-term (decades) effects relate to the effects of residue management on soil N fertility and soil physical and chemical properties, considering that these are affected by local climatic and soil conditions as well as land use and management. More targeted mitigation efforts for N2O emissions, after addition of crop residues to the soil, are urgently needed and require an improved methodology for emission accounting. This work needs to be underpinned by research to (1) develop and validate N2O emission factors for mature and immature crop residues, (2) assess emissions from belowground residues of terminated crops, (3) improve activity data on management of different residue types, in particular immature residues, and (4) evaluate long-term effects of residue addition on N2O emissions

Challenges of accounting nitrous oxide emissions from agricultural crop residues

Crop residues are important inputs of carbon (C) and nitrogen (N) to soils and thus directly and indirectly affect nitrous oxide (N2O) emissions. As the current inventory methodology considers N inputs by crop residues as the sole determining factor for N2O emissions, it fails to consider other underlying factors and processes. There is compelling evidence that emissions vary greatly between residues with different biochemical and physical characteristics, with the concentrations of mineralizable N and decomposable C in the residue biomass both enhancing the soil N2O production potential. High concentrations of these components are associated with immature residues (e.g., cover crops, grass, legumes, and vegetables) as opposed to mature residues (e.g., straw). A more accurate estimation of the short-term (months) effects of the crop residues on N2O could involve distinguishing mature and immature crop residues with distinctly different emission factors. The medium-term (years) and long-term (decades) effects relate to the effects of residue management on soil N fertility and soil physical and chemical properties, considering that these are affected by local climatic and soil conditions as well as land use and management. More targeted mitigation efforts for N2O emissions, after addition of crop residues to the soil, are urgently needed and require an improved methodology for emission accounting. This work needs to be underpinned by research to (1) develop and validate N2O emission factors for mature and immature crop residues, (2) assess emissions from belowground residues of terminated crops, (3) improve activity data on management of different residue types, in particular immature residues, and (4) evaluate long-term effects of residue addition on N2O emissions

Schwann Cell Precursors Generate the Majority of Chromaffin Cells in Zuckerkandl Organ and Some Sympathetic Neurons in Paraganglia

In humans, neurosecretory chromaffin cells control a number of important bodily functions, including those related to stress response. Chromaffin cells appear as a distinct cell type at the beginning of midgestation and are the main cellular source of adrenalin and noradrenalin released into the blood stream. In mammals, two different chromaffin organs emerge at a close distance to each other, the adrenal gland and Zuckerkandl organ (ZO). These two structures are found in close proximity to the kidneys and dorsal aorta, in a region where paraganglioma, pheochromocytoma and neuroblastoma originate in the majority of clinical cases. Recent studies showed that the chromaffin cells comprising the adrenal medulla are largely derived from nerve-associated multipotent Schwann cell precursors (SCPs) arriving at the adrenal anlage with the preganglionic nerve fibers, whereas the migratory neural crest cells provide only minor contribution. However, the embryonic origin of the ZO, which differs from the adrenal medulla in a number of aspects, has not been studied in detail. The ZO is composed of chromaffin cells in direct contact with the dorsal aorta and the intraperitoneal cavity and disappears through an autophagy-mediated mechanism after birth. In contrast, the adrenal medulla remains throughout the entire life and furthermore, is covered by the adrenal cortex. Using a combination of lineage tracing strategies with nerve- and cell type-specific ablations, we reveal that the ZO is largely SCP-derived and forms in synchrony with progressively increasing innervation. Moreover, the ZO develops hand-in-hand with the adjacent sympathetic ganglia that coalesce around the dorsal aorta. Finally, we were able to provide evidence for a SCP-contribution to a small but significant proportion of sympathetic neurons of the posterior paraganglia. Thus, this cellular source complements the neural crest, which acts as a main source of sympathetic neurons. Our discovery of a nerve-dependent origin of chromaffin cells and some sympathoblasts may help to understand the origin of pheochromocytoma, paraganglioma and neuroblastoma, all of which are currently thought to be derived from the neural crest or committed sympathoadrenal precursors

The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells : Implications for COVID-19 vascular research

Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is impor-tant to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, andin heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.Peer reviewe