(
A) Identification of putative TFBS for candidate upstream factors in Ciinte. Msx-up10 aligned with its counterpart from
C. savignyi. All putative sites for ventral factors (SBE, BRE, Tbx2/3, Nkxtun1, Nkx2-3/5/6 and Irx.c) and dorsal factors (Msx and Su(H)/Rbpj) have been mapped, but only conserved sites are shown: 4 BRE, 3 SBE, 1 Irx.c, 1 Tbx2/3 and 2 Msx. The region deleted in up2 and up11 abuts a BRE and contains a SBE; the loss of these sites might thus be responsible of the absence of activity in the VML. The region deleted in up8 and required for VDML activity contains 1 BRE, 1 Irx.c, 1 Tbx2/3 and 1 Msx sites. Note that the size of the highlighted site for of a given TF may vary depending on the matrix used. (
B) Working model for
Msx transcriptional regulation in the VDML.
Msx expression is initiated in DML precursors at the 64-cell stage (
Roure et al., 2014) through the proximal/early CRM (denoted b6.5 line, green) activated by Otx and Nodal (via Smad2/3). The Msx protein produced via this regulation would activate
Msx transcritption in the DML at gastrula/neurula stages via the distal/late CRM (denoted up10, orange). The same distal CRM would activate
Msx expression in the VML directly by Bmp signaling activated by the Admp ligand (via the SBEs and BREs) or Admp targets (Irx.c and Tbx2/3).