| First Author | Emechebe U | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27046536 | Mgi Jnum | J:232111 |
| Mgi Id | MGI:5776065 | Doi | 10.7554/eLife.07897 |
| Citation | Emechebe U, et al. (2016) T-box3 is a ciliary protein and regulates stability of the Gli3 transcription factor to control digit number. Elife 5:e07897 |
| abstractText | Crucial roles for T-box3 in development are evident by severe limb malformations and other birth defects caused by T-box3 mutations in humans. Mechanisms whereby T-box3 regulates limb development are poorly understood. We discovered requirements for T-box at multiple stages of mouse limb development and distinct molecular functions in different tissue compartments. Early loss of T-box3 disrupts limb initiation, causing limb defects that phenocopy Sonic Hedgehog (Shh) mutants. Later ablation of T-box3 in posterior limb mesenchyme causes digit loss. In contrast, loss of anterior T-box3 results in preaxial polydactyly, as seen with dysfunction of primary cilia or Gli3-repressor. Remarkably, T-box3 is present in primary cilia where it colocalizes with Gli3. T-box3 interacts with Kif7 and is required for normal stoichiometry and function of a Kif7/Sufu complex that regulates Gli3 stability and processing. Thus, T-box3 controls digit number upstream of Shh-dependent (posterior mesenchyme) and Shh-independent, cilium-based (anterior mesenchyme) Hedgehog pathway function. |
