Segregation of morphogenetic regulatory function of Shox2 from its cell fate guardian role in sinoatrial node development.

ABSTRACT: Shox2 plays a vital role in the morphogenesis and physiological function of the sinoatrial node (SAN), the primary cardiac pacemaker, manifested by the formation of a hypoplastic SAN and failed differentiation of pacemaker cells in Shox2 mutants. Shox2 and Nkx2-5 are co-expressed in the developing SAN and regulate the fate of the pacemaker cells through a Shox2-Nkx2-5 antagonistic mechanism. Here we show that simultaneous inactivation of Nkx2-5 in the SAN of Shox2 mutants (dKO) rescued the pacemaking cell fate but not the hypoplastic defects, indicating uncoupling of SAN cell fate determination and morphogenesis. Single-cell RNA-seq revealed that the presumptive SAN cells of Shox2^-/- mutants failed to activate pacemaking program but remained in a progenitor state preceding worki

SUBMITTER: Li H 

PROVIDER: S-EPMC10980793 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature