Tbx5 is dispensable for forelimb outgrowth.

[holt-oram syndrome]

Tbx 5 is essential for initiation of the forelimb , and its deletion in mice results in the failure of forelimb formation . Misexpression of dominant-negative forms of Tbx 5 results in limb truncations , suggesting Tbx 5 is also required for forelimb outgrowth . Here we show that Tbx 5 is expressed throughout the limb mesenchyme in progenitors of cartilage , tendon and muscle . Using a tamoxifeninducible Cre transgenic line , we map the time frame during which Tbx 5 is required for limb development . We show that deletion of Tbx 5 subsequent to limb initiation does not impair limb outgrowth . Furthermore , we distinguish two distinct phases of limb development : a Tbx 5 -dependent limb initiation phase , followed by a Tbx 5 -independent limb outgrowth phase . In humans , mutations in the T -box transcription factor TBX 5 are associated with the dominant disorder Holt-Oram syndrome (HOS ), which is characterised by malformations in the forelimb and heart . Our results demonstrate a short temporal requirement for Tbx 5 during early limb development , and suggest that the defects found in HOS arise as a result of disrupted TBX 5 function during this narrow time window .