Mechanistic Differences in the Transcriptional Interpretation of Local and Long-Range Shh Morphogen Signaling

作者：Oosterveen Tony^*; Kurdija Sanja; Alekseenko Zhanna; Uhde Christopher W; Bergsland Maria; Sandberg Magnus; Andersson Elisabet; Dias Jose M; Muhr Jonas; Ericson Johan

来源：Developmental Cell, 2012, 23(5): 1006-1019.

DOI：10.1016/j.devcel.2012.09.015

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.

• 出版日期2012-11-13