Thymosin-beta s (T beta s) are water-soluble peptides abundantly present in the cytoplasm and extracellular compartment. The functions of T beta s appear to be pleiotrophic, including actin-remodeling, wound healing, angiogenesis, etc. In the present study, we present the evidence that T beta s have anti-apoptotic activity on developing chick motoneurons (MNs) in vivo. Using in ovo electroporation, we introduced three isoforms of T beta (T beta 4, T beta 10, and T beta 15) and found the significantly diminished normal and limb bud removal (LBR)-induced programmed cell death. Such anti-apoptotic activity is independent of T beta's actin remodeling activity. On the other hand, overexpression of T beta s substantially reduced early cell death initiation signal, such as phosphorylation of c-Jun. Collectively, these results suggest that T beta s may prevent apoptosis of neurons via blockade of early apoptogenic signals independent of actin remodeling action. (c) 2006 Elsevier Inc. All rights reserved.