Fig. 9.

Regulatory interactions of the tbr control system. (A) An updated tbrain regulatory subcircuit showing the inputs into the γ(2) module from Ets1/2 and Erg identified in this study. The diagram displays interactions that occur in the SM prior to ingression. During this period the γ(2) module is inactive (due to the negative feedback from the erg gene) and tbr expression is controlled by modules C and α, the site of HesC spatial repression (see text). Network diagram was constructed in BioTapestry (Longabaugh et al., 2009). (B) Schematics showing proposed interactions of tbrain cis-regulatory modules in different embryonic territories. This model is based on the now commonly assumed mechanism of interactions between distant cis-regulatory modules by DNA looping. Between 15 and about 21hpf (Smith et al, 2008), dominant repression by HesC prevents tbrain expression outside of the skeletogenic micromere lineage. While Ets1/2 is present in the SM and then NSM during this period, tbrain activation in the PMCs occurs primarily through the C module due to the accumulation of the Erg repressor of γ(2) module in the SM, as in (A). By ingression, HesC expression has disappeared in the NSM (Smith and Davidson, 2008b), and for unknown reasons expression of erg is extinguished in the SM cells; Erg and Ets1/2 are now both present in NSM but only Ets1/2 in the post-ingression SM. The result is that the γ(2) module can now respond to SM Ets1/2 and contribute to tbr expression along with the module C booster, while γ(2) module is shut off in the NSM by Erg and the expression of tbr elsewhere continues to be excluded by HesC.