| First Author | Oosterveen T | Year | 2012 |
| Journal | Dev Cell | Volume | 23 |
| Issue | 5 | Pages | 1006-19 |
| PubMed ID | 23153497 | Mgi Jnum | J:191081 |
| Mgi Id | MGI:5460931 | Doi | 10.1016/j.devcel.2012.09.015 |
| Citation | Oosterveen T, et al. (2012) Mechanistic differences in the transcriptional interpretation of local and long-range Shh morphogen signaling. Dev Cell 23(5):1006-19 |
| abstractText | Morphogens orchestrate tissue patterning in a concentration-dependent fashion during vertebrate embryogenesis, yet little is known of how positional information provided by such signals is translated into discrete transcriptional outputs. Here we have identified and characterized cis-regulatory modules (CRMs) of genes operating downstream of graded Shh signaling and bifunctional Gli proteins in neural patterning. Unexpectedly, we find that Gli activators have a noninstructive role in long-range patterning and cooperate with SoxB1 proteins to facilitate a largely concentration-independent mode of gene activation. Instead, the opposing Gli-repressor gradient is interpreted at transcriptional levels, and, together with CRM-specific repressive input of homeodomain proteins, comprises a repressive network that translates graded Shh signaling into regional gene expression patterns. Moreover, local and long-range interpretation of Shh signaling differs with respect to CRM context sensitivity and Gli-activator dependence, and we propose that these differences provide insight into how morphogen function may have mechanistically evolved from an initially binary inductive event. |
