Fig. 8

Schematic representation of interactions between Lmx1 genes, the Wnt pathway and Rmst/mir-135a-2 [miR-135a]. a In the embryonic forebrain, canonical Wnt/beta-catenin pathway induces Rmst/mir-135a-2 [miR-135a], as well as the cortical hem determinant Lmx1a. miR-135a, in turn, negatively targets Wnt pathway mRNAs establishing an auto-regulatory loop. miR-135a is also predicted to target TGFβ/BMP pathway mRNAs as well as other targets. It is possible that the TGFβ/BMP pathway is also able to induce Rmst/mir-135a-2 [miR-135a] and establish a miR-135a/TGFβ/BMP auto-regulatory loop. It is also possible that Lmx1a contributes to Rmst/mir-135a-2 [miR-135a] expression. However, these interactions remain to be demonstrated. Ultimately, this complex network of positive and negative interactions plays a role in determining proper dorsal forebrain size (cortical hem, hippocampus primordium, choroid plexus and neocortex). b A similar scenario was previously identified in the embryonic midbrain [11] where Lmx1b drives the expression of Wnt1/Wnt pathway and of Rmst/mir-135a-2 [miR-135a], which in turn negatively modulates the levels of Lmx1b, Wnt1/Wnt pathway and other targets. Additionally, Wnt1/Wnt pathway and Lmx1a interactions have been demonstrated. All together these interactions are critical for midbrain dopamine progenitor pool patterning and expansion