The role of ectoderm in mouse digit development and regeneration
Description
The mouse digit tip possesses the capacity to fully regenerate the distal structures following amputation, representing a model for organ regeneration in the mammals. Adult mouse digits are known to regenerate following amputation at the distal level; the regenerative capacity of fetal digits correlates with the expression domain of the Msx1 gene in the digit. Previously we have provided the evidence that both Msx1 and Bmp4 are regulators of the regenerative response of the fetal digits. Using e15.5 digits, the data presented demonstrate that digit tip regeneration occurs in kidney capsule culture and that the ectodermal structures are dispensable for the ossification of the terminal phalanx but are required for the regeneration of the fetal mouse digit. Moreover, the roles of the ectoderm was characterized using in vitro organ culture, and it has been demonstrated that the ectoderm regulates digit regeneration through regulating cell dispersion, cell proliferation, cell survival, and endochondral differentiation, the lack of which results in abnormal distal bone formation and reduced elongation of the terminal phalanx. Using in vitro organ culture and micromass culture of e14.5 cells, it is also determined that the ectoderm is not required for the expression of the Msx1 gene at this stage, but is required for the dorsal shift of Msx1 expression domain in the mesenchyme during digit development. These results suggest that mouse fetal digit regeneration is regulated by the ectoderm, and that this mechanism is independent of the Msx1-Bmp4 pathway we described previously