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Background  Brain size and patterning are dependent on dosage-sensitive morphogen signaling pathways – yet how these pathways are calibrated remains enigmatic. Recent studies point to a new role for microRNAs in tempering the spatio-temporal range of morphogen functions during development. Here, we investigated the role of  miR-135a , derived from the  mir-135a-2  locus ,  in embryonic forebrain development.    Method  1. We characterized the expression of  miR-135a,  and its host gene  Rmst , by in situ hybridization ( ish ). 2. We conditionally ablated, or activated, beta-catenin in the dorsal forebrain to determine if this pathway was necessary and/or sufficient for  Rmst / miR-135a  expression. 3. We performed bioinformatics analysis to unveil the most predicted pathways targeted by  miR-135a.  4. We performed gain and loss of function experiments on  mir-135a-2  and analyzed by  ish  the expression of key markers of cortical hem, choroid plexus, neocortex and hippocampus.    Results  1.  miR-135a , embedded in the host long non-coding transcript  Rmst , is robustly expressed, and functional, in the medial wall of the embryonic dorsal forebrain, a Wnt and TGFβ/BMP-rich domain. 2. Canonical Wnt/beta-catenin signaling is critical for the expression of  Rmst  and  miR-135a , and the cortical hem determinant  Lmx1a . 3. Bioinformatics analyses reveal that the Wnt and TGFβ/BMP cascades are among the top predicted pathways targeted by  miR-135a . 4. Analysis of  mir-135a-2  null embryos showed that dorsal forebrain development appeared normal. In contrast, modest  mir-135a-2  overexpression, in the early dorsal forebrain, resulted in a phenotype resembling that of mutants with Wnt and TGFβ/BMP deficits - a smaller cortical hem and hippocampus primordium associated with a shorter neocortex as well as a less convoluted choroid plexus. Interestingly, late overexpression of  mir-135a-2  revealed no change.    Conclusions  All together, our data suggests the existence of a  Wnt/miR-135a  auto-regulatory loop, which could serve to limit the extent, the duration and/or intensity of the Wnt and, possibly, the TGFβ/BMP pathways.    Electronic supplementary material  The online version of this article (doi:10.1186/s13064-016-0065-y) contains supplementary material, which is available to authorized users.

Expression and functional analysis of the Wnt/beta-catenin induced mir-135a-2 locus in embryonic forebrain development