Fig. 4. Genetic interaction between Tbx6 and rib-vertebrae (rv). The genotypes are as indicated, except where `normal' is given to indicate that differences were not observed for embryos that were wild type, Tbx6^tm1Pa/+ or Dll1^tm1Gos+ in H. (A-E) Gross morphology and skeletal preparations of E15.5 embryos dissected from Tbx6^tm1Pa/+ x rv/rv matings. (A,B) Tbx6^tm1Pa/rv embryos are shorter in stature than their rv/+ littermates and have short tails (arrow in B indicates the tip of the tail). (C-E) Alcian Blue and Alizarin Red skeletal staining reveals fusions of the ribs and vertebrae along the entire AP axis of the Tbx6^tm1Pa/rv embryos. (E) High magnification of the skeleton in D shows that rib fusions occur both proximally and distally and that the neural arches of the lumbar region are fused along the axis. (F) Tbx6 expression in the tail regions of rv/rv and rv/+ E10.5 embryos. Dorsal (left) and side (right) views of the tails are shown. The tailbuds of the rv/rv mutant embryos are larger than the rv/+ littermates, and show diminished levels of Tbx6 transcripts compared with rv/+ tails. (G) The Tbx6 genomic locus showing the positions of the exons (blue boxes), start of transcription (black arrow), and the position and nature of the rv lesion. A red line indicates the Tbx6 genomic region that is duplicated and inverted (red arrow) in the rv mutation. The rv mutation is caused by the insertion of this duplicated and inverted region upstream of the Tbx6-coding region. (H-K) Alcian Blue and Alizarin Red skeletal preparations from E14.5 embryos dissected from Tbx6^tm1Pa/+ x Dll1^tm1Gos/+ crosses. (H) Heterozygous embryos for either Tbx6 or Dll1 showed normal skeletal morphology. (I) The genetic interaction between these two mutations can be seen in compound heterozygotes (labeled as Tbx6^+/– Dll1^+/–), which are characterized by the presence of abnormally formed vertebrae and ribs along the AP axis. (J,K) Higher magnifications of the Tbx6^tm1Pa/+ Dll1^tm1Gos/+ skeleton in I, the thoracic and lumbar region is shown in J, and the lumbar and sacral regions are shown in K. (J) A rib missing its proximal portion is indicated by a red arrowhead. Abnormally formed vertebrae are seen in thoracic vertebrae in (J, red arrow) and in the lumbar vertebrae in (K, red asterisks). Limbs have been removed from all skeletons.

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