Mab21l2 is required to promote cell proliferation in stylopods during early limb development

Mab2l12 is highly conserved across species and has been implicated in various developmental processes, including eye and heart development. Human patients and transgenic mice with MAB21L2(R51C) mutation have severe skeletal anomalies in their appendicular skeleton. In this study, we aimed to investigate the specific impact of Mab2l12 in limb development. By conditional gene knockout model, we found that removing Mab21l2 by Prx1-cre during early limb development led to malformation of the stylopods. Histological examination revealed a three-day delay of endochondral ossification in the Prx1-cre; Mab21l2^flox/flox mice. The critical window for Mab21l2 action in humerus development has been confined to E9.5-10.5 when Mab2l12 is expressed in the distal mesenchyme of forelimb buds. Reduced proliferation was noted in the chondrocytes of this perspective humerus region in Prx1-cre; Mab21l2^flox/flox mice at E10.5. This defect may contribute to a smaller cartilage template found at E13.5 and the subsequent humerus shortening at birth. These results imply that Mab21l2 is acting non-autonomously to control stylopods development.