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, Histological and immunological analyses

, Embryonic samples from timed matings (day of vaginal plug = E0.5) were collected, p.4

, Microtome sections of 7 µm thickness were examined histologically after periodic acid-Schiff staining. For immunofluorescent analysis, dewaxed and re-hydrated sections were treated in 10 mM Na citrate (pH 6) for 2 min in a pressure cooker and incubated for 2 hours in 3% BSA, 10% normal donkey serum (Jackson Laboratories), 0.1% Tween20 in PBS)

, Cy3-or Cy5-conjugated secondary antibodies (Jackson Laboratories), or AlexaFluor 488-, 594-or 647-conjugated secondary antibodies (Invitrogen), or Biotin-conjugated antibody, Tween20 in PBS and incubated overnight at 4°C. Relevant Cy2

. Streptavidin-cy3, After mounting (Hoechst, Invitrogen) images were taken on a Zeiss Axio ImagerZ1 (Axiocam MRM camera) and processed with Photoshop

, Immunofluorescent analysis on organ cultures was carried out as described previously 10

. Rt-qpcr,

, Total RNA was extracted from the dissected caudal area of urogenital ridges of Sox11 knockout and wildtype E10.75 embryos using the RNeasy MicroKit (Qiagen) followed by column DNase digestion to remove any contaminating genomic DNA, Samples (n=6) were reverse transcribed (M-MLV, Invitrogen) in combination with random primers. qPCR was performed using the TaqMan Master Kit (Roche) and a Light Cycler, vol.1

, Expression levels were normalized for Hprt. Primers were designed on the Roche Universal ProbeLibrary website

. Chip-qpcr, Kidneys were isolated from E14.5 wild-type embryos (OF1, purchased from Charles River) in PBS and kept on ice until dissociation with trypsin (Gibco) at 37°C. Cells were 1% formaldehyde-fixed, washed, and nuclei released in lysis buffer, p.140

, mM NaCl, 1 mM Edta, 1% Triton, 0,1% NaDeoxycholate, 0.4% SDS

S. Hpa000536, Wegner) or IgG, and protein-A sepharose beads, p.3391

, After extensive washes and elution, chromatine was purified using the QIAquick PCR purification columns (Qiagen) and quantified using the Qubit dsDNA HS Assay Kit

, For qPCR reactions, same DNA quantities (25 pg) or same volumes (1/50 of the eluats) were amplified with

. Sybrgreen, Roche) using primers located in the HS19-20 regulatory element of the protocadherin b cluster control region (CCR) or in the 3'UTR region of Cd24a gene as a negative control (Table S2). containing coding sequence (kind gift from P. Berta) were used for mutagenesis

, Mutations were introduced by site-directed mutagenesis into full-length human SOX11 plasmid using the

I. Quickchange and . Kit, Table 2) and subcloned into pcDNA3.1 expression vector (Life Technologies). The expression vector for the 12 nucleotides insertion variant (mut1063) was a kind gift from A. Morris 11 . For transient transfection, 12x10 4 HEK293 cells were plated per well of 24-well plates. Mixtures of 50 ng pCMV-Sport-?gal plasmid (Life Technologies), 50 ng pcDNA3.1-Sox11 expression plasmid, Stratagene) and primers listed in Suppl, vol.150

, Galactosidase and luciferase activities were assayed after 24 h using the ?-galactosidase Enzyme and Luciferase Assay System (Promega), respectively. Reporter activities were normalized for transfection efficiency

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