Embryonic and fetal limb myogenic cells are derived from developmentally distinct progenitors and have different requirements for β-catenin

Abstract

Vertebrate muscle arises sequentially from embryonic, fetal, and adult myoblasts. Although functionally distinct, it is unclear whether these myoblast classes develop from common or different progenitors. Pax3 and Pax7 are expressed by somitic myogenic progenitors and are critical myogenic determinants. To test the developmental origin of embryonic and fetal myogenic cells in the limb, we genetically labeled and ablated Pax3⁺ and Pax7⁺ cells. Pax3⁺Pax7⁻ cells contribute to muscle and endothelium, establish and are required for embryonic myogenesis, and give rise to Pax7⁺ cells. Subsequently, Pax7⁺ cells give rise to and are required for fetal myogenesis. Thus, Pax3⁺ and Pax7⁺ cells contribute differentially to embryonic and fetal limb myogenesis. To investigate whether embryonic and fetal limb myogenic cells have different genetic requirements we conditionally inactivated or activated β-catenin, an important regulator of myogenesis, in Pax3- or Pax7-derived cells. β-Catenin is necessary within the somite for dermomyotome and myotome formation and delamination of limb myogenic progenitors. In the limb, β-catenin is not required for embryonic myoblast specification or myofiber differentiation but is critical for determining fetal progenitor number and myofiber number and type. Together, these studies demonstrate that limb embryonic and fetal myogenic cells develop from distinct, but related progenitors and have different cell-autonomous requirements for β-catenin.