Table 1.
Gene Ontology Biological Process Terms Enriched in genes differentially expressed by Layer. Of 2633 genes that differed by layer relative to age and layer-matched samples (Fig 3; p.adj < 0.01; fold change > 2), 1217 were enriched in ectoderm and 1459 were enriched in mesenchyme. Gene Ontology Biological Process (GO-BP terms; Ashburner et al., 2000) that were enriched in genes differentially expressed at each age were identified using Database for Annotation, Visualization and Integrated Discovery (DAVID) functional annotation and clustering tools (D. W. Huang et al., 2009b; 2009a). Enriched terms were ranked by information content and p-value and filtered for redundancy (see Materials and Methods for details). The resulting top-ranked terms represented by genes in each layer are shown (blue for ectoderm, red for mesenchyme). Signaling-associated terms are highlighted in purple. Pop.Hits, number of mouse genes associated with the GO term; Count, number of differentially expressed genes associated with the GO term; Fold.Enrich, ratio of differentially expressed genes to all genes associated with GO term; p.adj, p-value after multiple testing correction (Benjamini and Hochberg, 1995); NA, terms were not enriched at this layer.
Ectoderm and mesenchyme gene functions based on enrichment in Gene Ontology Biological Process terms
| Gene Ontology Biological Process Term | Pop.hits | Ectoderm | Mesenchyme | Best Layer | ||||
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| count | fold.enrich | p.adjust | count | fold.enrich | p.adjust | |||
| GO:0001763~morphogenesis of a branching structure | 125 | 30 | 4.00 | 3.42EH08 | 33 | 3.58 | 2.85EH08 | both |
| GO:0045165~cell fate commitment | 147 | 29 | 3.29 | 3.50EH06 | 33 | 3.04 | 1.27EH06 | both |
| GO:0030334~regulation of cell migration | 92 | 17 | 3.08 | 2.68EH03 | 18 | 2.65 | 7.76EH03 | both |
| GO:0042573~retinoic acid metabolic process | 17 | 7 | 6.87 | 6.95EH03 | 6 | 4.78 | 8.27EH02 | both |
| GO:0031128~developmental induction | 21 | 5 | 3.97 | 2.94EH01 | 8 | 5.16 | 1.06EH02 | both |
|
| ||||||||
| GO:0002009~morphogenesis of an epithelium | 173 | 43 | 4.14 | 1.91EH12 | 33 | 2.58 | 4.17EH05 | Ect |
| GO:0022612~gland morphogenesis | 84 | 28 | 5.56 | 7.22EH11 | 17 | 2.74 | 7.97EH03 | Ect |
| GO:0007398~ectoderm development | 133 | 32 | 4.01 | 7.61EH09 | NA | NA | NA | Ect |
| GO:0042476~odontogenesis | 45 | 17 | 6.30 | 4.09EH07 | NA | NA | NA | Ect |
| GO:0030855~epithelial cell differentiation | 123 | 28 | 3.80 | 4.23EH07 | 16 | 1.76 | 2.92EH01 | Ect |
| GO:0045664~regulation of neuron differentiation | 102 | 25 | 4.09 | 6.12EH07 | 15 | 1.99 | 1.69EH01 | Ect |
| GO:0007242~intracellular signaling cascade | 915 | 99 | 1.80 | 9.35EH07 | 88 | 1.30 | 9.48EH02 | Ect |
| GO:0007431~salivary gland development | 31 | 14 | 7.53 | 9.63EH07 | 7 | 3.06 | 2.14EH01 | Ect |
| GO:0043583~ear development | 104 | 24 | 3.85 | 3.42EH06 | 20 | 2.61 | 4.46EH03 | Ect |
| GO:0007156~homophilic cell adhesion | 117 | 23 | 3.28 | 8.06EH05 | 21 | 2.43 | 7.28EH03 | Ect |
| GO:0060562~epithelial tube morphogenesis | 111 | 22 | 3.30 | 1.16EH04 | 17 | 2.07 | 9.17EH02 | Ect |
| GO:0016055~Wnt receptor signaling pathway | 130 | 24 | 3.08 | 1.25EH04 | 21 | 2.19 | 2.33EH02 | Ect |
| GO:0001942~hair follicle development | 50 | 14 | 4.67 | 2.47EH04 | NA | NA | NA | Ect |
| GO:0007223~Wnt receptor signaling pathway, calcium modulating pathway | 20 | 9 | 7.50 | 4.41EH04 | NA | NA | NA | Ect |
| GO:0016331~morphogenesis of embryonic epithelium | 78 | 17 | 3.63 | 4.89EH04 | 12 | 2.08 | 2.39EH01 | Ect |
| GO:0060512~prostate gland morphogenesis | 27 | 10 | 6.17 | 6.21EH04 | 6 | 3.01 | 3.35EH01 | Ect |
| GO:0048638~regulation of developmental growth | 37 | 11 | 4.96 | 1.39EH03 | 8 | 2.93 | 1.67EH01 | Ect |
| GO:0031076~embryonic camera-type eye development | 15 | 7 | 7.78 | 3.45EH03 | 5 | 4.52 | 1.95EH01 | Ect |
| GO:0001738~morphogenesis of a polarized epithelium | 11 | 6 | 9.09 | 5.89EH03 | NA | NA | NA | Ect |
| GO:0001736~establishment of planar polarity | 5 | 4 | 13.34 | 3.35EH02 | NA | NA | NA | Ect |
| GO:0030509~BMP signaling pathway | 24 | 7 | 4.86 | 3.98EH02 | NA | NA | NA | Ect |
| GO:0040036~regulation of fibroblast growth factor receptor signaling pathway | 11 | 5 | 7.58 | 4.78EH02 | NA | NA | NA | Ect |
|
| ||||||||
| GO:0048705~skeletal system morphogenesis | 130 | 15 | 1.92 | 2.33EH01 | 39 | 4.06 | 2.02EH11 | Mes |
| GO:0030198~extracellular matrix organization | 101 | 14 | 2.31 | 9.50EH02 | 34 | 4.56 | 2.43EH11 | Mes |
| GO:0051216~cartilage development | 78 | 15 | 3.21 | 4.59EH03 | 29 | 5.04 | 1.19EH10 | Mes |
| GO:0001525~angiogenesis | 133 | 23 | 2.88 | 4.98EH04 | 37 | 3.77 | 6.96EH10 | Mes |
| GO:0016477~cell migration | 240 | 29 | 2.01 | 1.16EH02 | 51 | 2.88 | 1.90EH09 | Mes |
| GO:0035107~appendage morphogenesis | 115 | 16 | 2.32 | 5.47EH02 | 33 | 3.89 | 3.38EH09 | Mes |
| GO:0007409~axonogenesis | 163 | 26 | 2.66 | 5.05EH04 | 39 | 3.24 | 1.33EH08 | Mes |
| GO:0008284~positive regulation of cell proliferation | 284 | 38 | 2.23 | 3.10EH04 | 54 | 2.58 | 2.51EH08 | Mes |
| GO:0060537~muscle tissue development | 136 | 17 | 2.08 | 9.66EH02 | 33 | 3.29 | 2.39EH07 | Mes |
| GO:0048010~vascular endothelial growth factor receptor signaling pathway | 14 | NA | NA | NA | 11 | 10.64 | 2.78EH07 | Mes |
| GO:0010811~positive regulation of cell-substrate adhesion | 27 | NA | NA | NA | 14 | 7.02 | 8.93EH07 | Mes |
| GO:0007169~transmembrane receptor protein tyrosine kinase signaling pathway | 192 | 26 | 2.26 | 4.73EH03 | 38 | 2.68 | 2.57EH06 | Mes |
| GO:0014032~neural crest cell development | 33 | 10 | 5.05 | 2.65EH03 | 13 | 5.34 | 7.13EH05 | Mes |
| GO:0002062~chondrocyte differentiation | 21 | NA | NA | NA | 10 | 6.45 | 2.50EH04 | Mes |
| GO:0030111~regulation of Wnt receptor signaling pathway | 39 | 7 | 2.99 | 2.58EH01 | 13 | 4.52 | 4.19EH04 | Mes |
| GO:0050921~positive regulation of chemotaxis | 11 | NA | NA | NA | 7 | 8.62 | 1.42EH03 | Mes |
| GO:0001756~somitogenesis | 41 | NA | NA | NA | 12 | 3.97 | 3.26EH03 | Mes |
| GO:0010464~regulation of mesenchymal cell proliferation | 23 | 6 | 4.35 | 1.25EH01 | 9 | 5.30 | 3.70EH03 | Mes |
| GO:0048634~regulation of muscle development | 43 | 7 | 2.71 | 3.36EH01 | 12 | 3.78 | 4.92EH03 | Mes |
| GO:0060638~mesenchymal-epithelial cell signaling | 6 | NA | NA | NA | 5 | 11.29 | 8.34EH03 | Mes |
| GO:0048565~gut development | 39 | 6 | 2.56 | 5.04EH01 | 11 | 3.82 | 8.38EH03 | Mes |
| GO:0007229~integrin-mediated signaling pathway | 76 | NA | NA | NA | 15 | 2.67 | 2.12EH02 | Mes |
| GO:0050679~positive regulation of epithelial cell proliferation | 31 | NA | NA | NA | 9 | 3.93 | 2.47EH02 | Mes |