Figure S1: Deletion of Dlx3 in the NC A) LacZ staining of Dlx3 LacZ/WT mice (a) and Wnt1- cre:r26r LacZ mice (b) at E11.5. The arrowhead points at

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Figure S1: Deletion of Dlx3 in the NC A) LacZ staining of Dlx3 LacZ/WT mice (a) and Wnt1- cre:r26r LacZ mice (b) at E11.5. The arrowhead points at Dlx3 expression in the branchial arches.

1 Figure S1: Deletion of Dlx3 in the NC A) LacZ staining of Dlx3 LacZ/WT mice (a) and Wnt1- cre:r26r LacZ mice (b) at E11.5. The arrowhead points at Dlx3 expression in the branchial arches. B) PCR and Southern blot analysis of genomic DNA from the head of E11.5 embryos: Dlx3 F/WT (1), Dlx3 F/LacZ (2), Wnt1- cre:dlx3 F/WT (3), Wnt1- cre:dlx3 F/LacZ (4). Four Dlx3 alleles are indicated: Dlx3 WT, Dlx3 LacZ, Dlx3 F and the recombined allele Dlx3 Δ F. C) qpcr analysis of Dlx3 mrna levels in the head of E11.5 embryos. T- test, n=3.

Figure S2: Dlx3 expression in the developing root Dlx3 expression during radiculogenesis of the first molar at P15. Immunohistochemical analysis using anti- Dlx3 antibody on molar section.

2 Figure S2: Dlx3 expression in the developing root Dlx3 expression during radiculogenesis of the first molar at P15. Immunohistochemical analysis using anti- Dlx3 antibody on molar section. Black arrows indicate odontoblasts. Black arrowheads indicate cementoblasts. White arrowheads indicate the HERS. DP, dental pulp; D, dentin; B, bone; MC, Meckel s cartilage. Scale bar 100 µm.

Figure S3: Ameloblast differentiation and enamel formation in Wnt1- cre:dlx3 F/LacZ mice A) Immunohistochemical analysis of Dlx3 expression in mandibular incisors (cross sections) from WT and cko

3 Figure S3: Ameloblast differentiation and enamel formation in Wnt1- cre:dlx3 F/LacZ mice A) Immunohistochemical analysis of Dlx3 expression in mandibular incisors (cross sections) from WT and cko mice at P5, showing that Dlx3 remains expressed in the ameloblasts of cko mice. B) Frontal section of incisor from cko mouse at P15. Ameloblast (Am) followed their normal life- cycle in cko mice, from presecretion to secretion to maturation stage shown here. The structure of ameloblasts was normal, evidencing a ruffled border (arrowheads). The respective morphology of external aprismatic (eae), external prismatic (epe) and internal prismatic (ipe) enamel was not affected. Prism decussation was not altered (horizontal arrows). Scale 100 µm. C) Scanning electron microscopy analysis of the enamel of mandibular incisors (maturation zone) from WT and cko mice at 8 weeks. B, bone; D, dentin; E, enamel. D) Scanning electron microscopy of first mandibular molars from WT and cko mice at 8 weeks.

Figure S4: Primary mandibular cell culture and Dlx3 expression A) Phase contrast observation of cells isolated from mandibles at P0 used for ChIP- seq analysis.

4 Figure S4: Primary mandibular cell culture and Dlx3 expression A) Phase contrast observation of cells isolated from mandibles at P0 used for ChIP- seq analysis. The mixed population of cells includes: osteoblasts (a), cells from the dental epithelium (b), and cells from the dental mesenchyme (c). B) RT- PCR analysis of the expression of Rs15 and Dlx3 in primary cells isolated from mouse mandibles at P0.

5 Table S1: Microarray analysis of mandibles from Wnt1-cre:Dlx3F/LacZ (cko) and WT mice Gene Symbol RefSeq Transcript ID p-value(cko vs. WT) Fold-Change(cKO vs. WT) Lce1c NM_ Dspp NM_ Dlx3 NM_ Sprr1b NM_ Lce1f NM_ Krt1 NM_ Lce1d NM_ Hrnr NM_ /// XM_ /// XM_ Krt10 NM_ Lce1b NM_ Mmp20 NM_ Lce1a1 NM_ Gm94 NM_ Mpzl2 NM_ Lyg1 NM_ Lce1a2 NM_ Lce1a1 NM_ Flg XM_ /// XM_ /// XM_ Il1f5 NM_ /// NM_ /// NM_ Lce1i NM_ L13Rik XM_ /// XM_ Tmf1 NM_ Sost NM_ Calb1 NM_ Klk4 NM_ Sprr2h NM_ Mepe NM_ Enam NM_ Krt27 NM_ Ptprr NM_ /// NM_ /// NM_ /// NM_ Calb1 NM_ Serpina9 NM_ Acpp NM_ /// NM_ Calb1 NM_ Steap1 NM_ Cfd NM_ Krt16 NM_ Kprp NM_ Gng4 NM_ Sox21 NM_ Krt24 NM_ Ckmt1 NM_ Hal NM_ Aifm3 NM_ Clu /// LOC NM_ /// XM_ Mpzl2 NM_ Lama3 NM_ /// XM_ /// XM_ Lamb3 NM_ Gchfr NM_ Gal3st4 NM_ Tspan8 NM_ /// NM_ /// NM_ Papln NM_ Msi2 NM_ /// XM_ Calb1 NM_ Thy1 NM_ Acpp NM_ /// NM_ Slurp1 NM_ Lce1c /// Lce1f /// Lce1g NM_ /// NM_ /// NM_ Gng4 NM_ Aplp1 NM_ Ckmt1 NM_ Mpzl2 NM_ Fam84a NM_ Fetub NM_ /// NM_ /// NM_ Grik1 NM_ /// NM_ H2-K1 NM_ Rsad1 NM_ H2afv NM_ /// XM_ /// XM_ Bglap /// Bglap-rs1 /// Bglap2 NM_ /// NM_ /// NM_ /// NM_ Ildr2 NM_ /// XM_ /// XM_ Magi2 NM_ /// NM_ /// NM_ Fgf1 NM_ Pmch NM_ H2afv NM_ /// XM_ /// XM_ Clu /// LOC NM_ /// XM_ Taf15 NM_ Rgs4 NM_ Ctsw NM_ Acpp NM_ /// NM_ Myo5b NM_ Gabrb2 NM_ Gabrb2 NM_ Clu /// LOC NM_ /// XM_ Lipc NM_ Plekhh1 NM_ /// XM_ /// XM_ Nebl NM_ Galnt12 NM_ Lrrc8e NM_ Bnc1 NM_ Aplp1 NM_ Cxcl14 NM_ Pla2g5 NM_ /// NM_

6 Sfn NM_ LOC /// Plxnc1 NM_ /// XM_ Dtna NM_ /// NM_ Ildr2 NM_ /// XM_ /// XM_ Cxadr NM_ /// NM_ Frmd5 NM_ Acer1 NM_ Sp6 NM_ Tulp2 NM_ /// NM_ Msx2 NM_ Cadps2 NM_ Celsr1 NM_ Acpl2 NM_ Ankrd6 NM_ /// NM_ /// NM_ Slc20a2 NM_ LOC /// Tesc NM_ /// XM_ Sp6 NM_ Cyp26a1 NM_ D3Bwg0562e NM_ Chdh NM_ /// NM_ /// NM_ Chst1 NM_ Sema3e NM_ Ovol1 NM_ Dhcr24 NM_ H2-D1 /// H2-K1 /// LOC NM_ /// NM_ /// XM_ /// XM_ Fbln7 NM_ Ctnnd2 /// LOC NM_ /// XR_ St8sia1 NM_ St8sia1 NM_ Satb1 NM_ /// NM_ /// NM_ /// NM_ Amtn NM_ /// XM_ /// XM_ Ddx6 NM_ /// NM_ /// NM_ Ccdc109b NM_ P10Rik NM_ /// NM_ Vangl2 NM_ Bmp7 NM_ Ndrg1 NM_ AI NR_ /// XR_ /// XR_ Ahnak2 NM_ /// XM_ Sft2d3 NM_ /// XM_ /// XM_ LOC /// Tmem20 NM_ /// XM_ Fgfr1 NM_ /// NM_ /// NM_ Gpr115 NM_ /// XM_ /// XM_ Dsc3 NM_ Kcnk2 NM_ /// NM_ /// NR_ Dner NM_ Tspan7 NM_ Col17a1 NM_ Itgb8 NM_ Cdc42ep3 NM_ Rps25 NM_ Mbp NM_ /// NM_ /// NM_ /// NM_ Cuedc1 NM_ /// NM_ Galnt3 NM_ /// XM_ /// XM_ Kcnq1ot1 NR_ Rasgrp2 NM_ Fzd8 NM_ Insig2 NM_ /// NM_ Gas5 NR_ Mia1 NM_ LOC /// Nr2f1 NM_ /// XM_ Sorbs1 NM_ /// NM_ /// NM_ /// NM_ Mbp NM_ /// NM_ /// NM_ /// NM_ Agt NM_ Tm6sf1 NM_ Slc25a34 NM_ Matn3 NM_ Cytl1 NM_ Hapln1 NM_ Ihh NM_ F5 NM_ Tpm3 NM_ Adamts18 NM_ Lgals2 NM_ Comp NM_ Kif5b NM_ Myh7 NM_ Tpm3 NM_ Kcnma1 NM_ Myl3 NM_ Slc30a2 NM_ Mbp NM_ /// NM_ /// NM_ /// NM_ Myl3 NM_ Chad NM_ Tns3 NM_ Myl3 NM_ Expi NM_ Hba-a1 /// Hba-a2 NM_ /// NM_ Mbp NM_ /// NM_ /// NM_ /// NM_ Gm6293 /// Uqcr10 NM_ /// XM_ Dcpp1 NM_ Gm6293 /// Uqcr10 NM_ /// XM_ Dcpp1 /// Dcpp2 /// Dcpp3 /// LOC NM_ /// NM_ /// NM_ /// XM_

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NES: normalized enrichment score (analyzed using KEGG pathway gene sets in the GSEA software); FDR:

NES: normalized enrichment score (analyzed using KEGG pathway gene sets in the GSEA software); FDR: Supplementary table1. List of gene sets with simultaneously altered the enrichment upon SAP18 overexpression and knockdown. Gene sets enriched by SAP18 and reduced by shsap18 SAP18 against LacZ shsap18