Novel molecular insights into human tooth agenesis

The development of dentition is a fascinating process that involves a complex series of epithelial-mesenchymel signaling interactions. That such a precise process frequently goes awry is not surprising. Indeed, tooth agenesis is one of the most commonly inherited disorders in humans that affects up to twenty percent of the population and imposes significant functional, emotional and financial burdens on patients. Mutations in the paired box domain containing transcription factor PAX9 result in autosomal dominant tooth agenesis that primarily involves posterior dentition. Despite these advances, little is known about how PAX9 mediates key signaling actions in tooth development and how aberrations in PAX9 functions lead to tooth agenesis. As an initial step towards providing evidence for the pathogenic role of mutant PAX9 proteins, I performed a series of molecular genetic analyses aimed at resolving the structural and functional defects produced by a number of PAX9 mutations causing non-syndromic posterior tooth agenesis. It is likely that the pathogenic mechanism underlying tooth agenesis for the first two mutations studied (219InsG and IIe87Phe) is haploinsufficiency. For the six paired domain missense mutations studied, the lack of functional defects observed for three of the mutant proteins suggests that these mutations altered PAX9 function through alternate mechanisms. Next, I explored further the nature of the partnership between Pax9 and the Msx1 homeoprotein and their role in the expression of a downstream effector molecule, Bmp4. When viewed in the context of events occurring in dental mesenchyme, the results of these studies indicate that the Pax9-Msx1 protein interaction involves the localized up-regulation of Bmp4 activity that is mediated by synergistic interactions between the two transcription factors. Importantly, these assays corroborate in vivo data from mouse genetic studies and support reports of Pax9-dependent expression of Bmp4 in dental mesenchyme. Taken together, these results suggest that PAX9 mutations cause an early developmental defect due to an inability to maintain the inductive potential of dental mesenchyme through involvement in a pathway involving Msx1 and Bmp4. ^

Mineral nitrogen from KCl extractions of soil from the Jena Experiment (Main Experiment up to 30cm depth, year 2002)

As an estimate of plant-available N, this data set contains measurements of inorganic nitrogen (NO3-N and NH4-N, the sum of which is termed mineral N or Nmin) determined by extraction with 1 M KCl solution of soil samples from the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. Soil sampling and analysis: Five soil cores (diameter 0.01 m) were taken at a depth of 0 to 0.15 m and 0.15 to 0.3 m of the mineral soil from each of the experimental plots in September 2002. Samples of the soil cores per plot were pooled during each sampling campaign. NO3-N and NH4-N concentrations were determined by extraction of soil samples with 1 M KCl solution and were measured in the soil extract with a Continuous Flow Analyzer (CFA, Skalar, Breda, Netherlands).

Mineral nitrogen from KCl extractions of soil from the Jena Experiment (Main Experiment up to 30cm depth, year 2004)

As an estimate of plant-available N, this data set contains measurements of inorganic nitrogen (NO3-N and NH4-N, the sum of which is termed mineral N or Nmin) determined by extraction with 1 M KCl solution of soil samples from the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. Soil sampling and analysis: Five soil cores (diameter 0.01 m) were taken at a depth of 0 to 0.15 m and 0.15 to 0.3 m of the mineral soil from each of the experimental plots in March and October 2004. Samples of the soil cores per plot were pooled during each sampling campaign. NO3-N and NH4-N concentrations were determined by extraction of soil samples with 1 M KCl solution and were measured in the soil extract with a Continuous Flow Analyzer (CFA, Skalar, Breda, Netherlands).

Mineral nitrogen from KCl extractions of soil from the Jena Experiment (Main Experiment up to 15cm depth, year 2005)

As an estimate of plant-available N, this data set contains measurements of inorganic nitrogen (NO3-N and NH4-N, the sum of which is termed mineral N or Nmin) determined by extraction with 1 M KCl solution of soil samples from the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. Soil sampling and analysis: Five soil cores (diameter 0.01 m) were taken at a depth of 0 to 0.15 m of the mineral soil from each of the experimental plots in April and September 2005. Samples of the soil cores per plot were pooled during each sampling campaign. NO3-N and NH4-N concentrations were determined by extraction of soil samples with 1 M KCl solution and were measured in the soil extract with a Continuous Flow Analyzer (CFA, Skalar, Breda, Netherlands).

Major, trace element and XRF data for sediments and fish tooth samples, from a shallow marine setting with varying redox conditions (Site U1356, Wilkes Land Margin, E.Antarctica)

Fossil fish teeth from pelagic open ocean settings are considered a robust archive for preserving the neodymium (Nd) isotopic composition of ancient seawater. However, using fossil fish teeth as an archive to reconstruct seawater Nd isotopic compositions in different sedimentary redox environments and in terrigenous-dominated, shallow marine settings is less proven. To address these uncertainties, fish tooth and sediment samples from a middle Eocene section deposited proximal to the East Antarctic margin at Integrated Ocean Drilling Program Site U1356 were analyzed for major and trace element geochemistry, and Nd isotopes. Major and trace element analyses of the sediments reveal changing redox conditions throughout deposition in a shallow marine environment. However, variations in the Nd isotopic composition and rare earth element (REE) patterns of the associated fish teeth do not correspond to redox changes in the sediments. REE patterns in fish teeth at Site U1356 carry a typical mid-REE-enriched signature. However, a consistently positive Ce anomaly marks a deviation from a pure authigenic origin of REEs to the fish tooth. Neodymium isotopic compositions of cleaned and uncleaned fish teeth fall between modern seawater and local sediments and hence could be authigenic in nature, but could also be influenced by sedimentary fluxes. We conclude that the fossil fish tooth Nd isotope proxy is not sensitive to moderate changes in pore water oxygenation. However, combined studies on sediments, pore waters, fish teeth and seawater are needed to fully understand processes driving the reconstructed signature from shallow marine sections in proximity to continental sources. This article is protected by copyright. All rights reserved.

Mineral nitrogen from KCl extractions of soil from the Jena Experiment (Main Experiment up to 15cm depth, year 2008)

As an estimate of plant-available N, this data set contains measurements of inorganic nitrogen (NO3-N and NH4-N, the sum of which is termed mineral N or Nmin) determined by extraction with 1 M KCl solution of soil samples from the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. Soil sampling and analysis: Five soil cores (diameter 0.01 m) were taken at a depth of 0 to 0.15 m of the mineral soil from each of the experimental plots in March and October 2008. In October 2008, also the plots of the management experiment, that altered mowing frequency and fertilized subplots (see further details below) were sampled. Samples of the soil cores per plot (subplots in case of the management experiment) were pooled during each sampling campaign. NO3-N and NH4-N concentrations were determined by extraction of soil samples with 1 M KCl solution and were measured in the soil extract with a Continuous Flow Analyzer (CFA, AutoAnalyzer, Seal, Burgess Hill, United Kingdom).

Mineral nitrogen from KCl extractions of soil from the Jena Experiment (Main Experiment up to 15cm depth, year 2006)

As an estimate of plant-available N, this data set contains measurements of inorganic nitrogen (NO3-N and NH4-N, the sum of which is termed mineral N or Nmin) determined by extraction with 1 M KCl solution of soil samples from the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. Soil sampling and analysis: Five soil cores (diameter 0.01 m) were taken at a depth of 0 to 0.15 m of the mineral soil from each of the experimental plots in March 2006. In October 2006 also the plots of the management experiment, that altered mowing frequency and fertilized subplots (see further details below) were sampled. Measurements from the management experiment are separated into 0 to 0.08 m and 0.08 to 0.15 m. Samples of the soil cores per plot (subplots in case of the management experiment) were pooled during each sampling campaign. NO3-N and NH4-N concentrations were determined by extraction of soil samples with 1 M KCl solution and were measured in the soil extract with a Continuous Flow Analyzer (CFA, AutoAnalyzer, Seal, Burgess Hill, United Kingdom).

Mineral nitrogen from KCl extractions of soil from the Jena Experiment (Main Experiment up to 15cm depth, year 2007)

As an estimate of plant-available N, this data set contains measurements of inorganic nitrogen (NO3-N and NH4-N, the sum of which is termed mineral N or Nmin) determined by extraction with 1 M KCl solution of soil samples from the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. Soil sampling and analysis: Five soil cores (diameter 0.01 m) were taken at a depth of 0 to 0.15 m of the mineral soil from each of the experimental plots in March and October 2007. In March and in October 2007 also the plots of the management experiment, that altered mowing frequency and fertilized subplots (see further details below) were sampled. Samples of the soil cores per plot (subplots in case of the management experiment) were pooled during each sampling campaign. NO3-N and NH4-N concentrations were determined by extraction of soil samples with 1 M KCl solution and were measured in the soil extract with a Continuous Flow Analyzer (CFA, AutoAnalyzer, Seal, Burgess Hill, United Kingdom).

Mineral nitrogen from KCl extractions of soil from the Jena Experiment (Main Experiment up to 30cm depth, year 2003)

As an estimate of plant-available N, this data set contains measurements of inorganic nitrogen (NO3-N and NH4-N, the sum of which is termed mineral N or Nmin) determined by extraction with 1 M KCl solution of soil samples from the main experiment plots of a large grassland biodiversity experiment (the Jena Experiment; see further details below). In the main experiment, 82 grassland plots of 20 x 20 m were established from a pool of 60 species belonging to four functional groups (grasses, legumes, tall and small herbs). In May 2002, varying numbers of plant species from this species pool were sown into the plots to create a gradient of plant species richness (1, 2, 4, 8, 16 and 60 species) and functional richness (1, 2, 3, 4 functional groups). Plots were maintained by bi-annual weeding and mowing. Soil sampling and analysis: Five soil cores (diameter 0.01 m) were taken at a depth of 0 to 0.15 m and 0.15 to 0.3 m of the mineral soil from each of the experimental plots in March, June, and October 2003. Samples of the soil cores per plot were pooled during each sampling campaign. NO3-N and NH4-N concentrations were determined by extraction of soil samples with 1 M KCl solution and were measured in the soil extract with a Continuous Flow Analyzer (CFA, Skalar, Breda, Netherlands).