Fig. 6: Regulatory elements bound by Meis, Tbx, and Hox factors control Fgf10 expression at limb initiation.
From: Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors
a Fgf10 expression at E9.5 and E10.5 in embryos with the CRISPR/Cas9-mediated-targeted Meis deletions indicated in c. Solid arrowheads indicate Fgf10 expression domain in FLs. Asterisks indicate non-limb Fgf10 expression domains. Empty arrowhead indicates the specific absence of Fgf10 expression in the anterior limb bud. Limbs analyzed: N = 12 for 5′−0.4∆, N = 10 for 3′−0.4∆, and N = 8 for 14.5∆. Scale bars = 100 μm in FLs and 1000 μm in whole embryos. b Quantitative RT-PCR showing a reduction of Fgf10 transcripts in E9.5 FL buds of embryos with the indicated regulatory region deletions. Limbs analyzed: For 5′−0.4∆, N = 7; For 3′−0.4∆, N = 8. For 14.5∆, N = 6. Two-tailed, one-sample t-test. Exact p-values from left to right: 0.0037; 0.0013; 0.0081 respectively. Red bars represent median values. c Examples of limb skeletons of genetic combinations between Meis mutants and Fgf10 regulatory region deletions. Scale bar = 1000 μm. d Comparison of pelvis and femur length in genetic combinations of Meis mutants and Fgf10 regulatory region deletions. Two-tailed, unpaired Mann–Whitney test. Limbs analyzed: M1HTM2KO N = 10; M1HTM2KO;5′−0.4∆, N = 6; M1HTM2KO;14.5∆, N = 4. Exact p-values from left to right: 0.3132; 0.0759; 0.0019; 0.0020. Red bars represent mean values. e Examples of limb skeletons of genetic combinations between Meis mutants and Fgf10 regulatory region deletions, showing the limb AP axis. Scale bar = 1000 μm. f Scoring of skeletal element loss in the genetic combinations of Meis mutants and Fgf10 regulatory region deletions shown in c. Loss of each skeletal element (fibula or digit) scores 1. Embryos analyzed: M1HTM2KO N = 10; M1HTM2KO;5′−0.4∆, N = 6; M1HTM2KO;14.5∆, N = 4; 14.5∆ N = 12; 5′−0.4∆, N = 8. Two-tailed, unpaired Mann–Whitney test. Exact p-values from top to down and left to right: 0.0357; 0.0245; 0.0360; 0.0005. Red bars represent mean values. ns, non-significant; *p < 0.05, **p < 0.01, ***p < 0.001. Statistics were not adjusted for multiple comparisons. Source data are provided as a Source Data file. Source images are available at Mendeley Data80 [https://data.mendeley.com/datasets/r774bxyf8d/2].
