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. 2024 Jun 3;151(11):dev202722. doi: 10.1242/dev.202722

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© 2024. Published by The Company of Biologists Ltd

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Fig. 4. — Tbx3 and Hand2 cooperatively control posterior limb skeletal identities and co-regulate shared target genes in early limb buds. (A-C) Skeletal analysis of wild-type (Wt), Hand2-deficient (A), Tbx3^Δ/Δc (B) and Tbx3^Δ/ΔcHand2^Δ/+ (C) mouse forelimbs (E14.5). The genetic interaction of Tbx3 and Hand2 regulates posterior limb skeletal elements (ulna and posterior digits; C). The number of embryos exhibiting the illustrated phenotype is indicated at the bottom of each panel. Digit identities are indicated from anterior to posterior (1-5). Asterisks indicate digit malformations. Scale bars: 500 µm. (D) RNA-FISH analysis of forelimb buds (n=4 biological replicates per genotype; E10.0; 29-32 somites). All limb buds are oriented with anterior to the top and posterior to the bottom. Scale bar: 200 µm. (E) TBX3 and HAND2 share a small subset of their target genes (n=31). (F) Heatmap of the target genes co-regulated by TBX3 and HAND2. Genes in bold have known functions in early limb buds. Asterisks indicate that Shh and Gli3 are manually curated target genes.