Reply to Kelder et al.: Does the dorsal mesenchymal protrusion act as a temporary pacemaker during heart development?

We thank Kelder et al. (1) for sharing their valuable insights into the development of atrioventricular (AV) junction. In response to their comments, our replies are as follows. The anatomical identity of the derivatives of dorsal mesenchymal protrusion (DMP) in our studies is in agreement with that described previously (2–5), which can be mapped by Mef2c-AHF-Cre (3, 5), and was also shown to be overlapped with Shox2 expression (2). We also found that Shox2 is co-expressedwithHcn4,Nkx2–5, and cTnT in theDMPderivatives at E11.0 (Fig. 1). The origin of cells that contribute to the compact AV node (AVN) is still controversial. In the letter by Kelder et al. (1), the authors argued that the CTNI /HCN4 /ISL1 domain shown in the accompanying figure represents the putative AVN region. However, fate mapping by Isl1-Cre identified only a small subset of AVN cells that are derived from Isl1-expressing cells (6). Thus, whether the CTNI /HCN4 /ISL1 domain described by the authors is the primordial AVN warrants further validation.