03-P110 Limb muscle and tendon patterning requires timed activity of Tbx4 and Tbx5

Gene regulatory networks are key elements for understanding how the different central nervous system regions differentiate. In recent years our group has done an extensive molecular characterization of the chicken pretectal region, obtaining a precise map of AP and DV molecular codes with respect to differential histogenetic pattern (Ferran et al., 2007; 2009, in press). As in other CNS regions, such as the spinal cord, Bmps signals from the roof plate and Shh signals from the floor and basal plates are clearcut candidates for governing the dorso-ventral patterning of the pretectum. The Msx1 transcription factor plays a role in diencephalic development, acting as intermediary between Bmp and Wnt (Bach et al., 2006), but it is still unclear how its expression is controlled by the gene regulatory network. Regulatory modules can be located in introns, exons or non-coding DNA regions, sometimes far away from the gene. In this work, we used comparative analysis of genomes to identify several highly-conserved non-coding DNA regions (HCNRs) located upstream and downstream of Msx1, and tested their ability for regulating Msx1 expression specifically in the pretectal region. This kind of approach is necessary for illuminating the specific regulatory network that patterns dorsoventral subdivisions in the pretectum, and possibly also in other CNS domains. Supported by NIH Grant 1-R01-MH070370-01A2, CIBERER (FISMinistry of Health), and MEC grant BFU2005-09378-C02-01 to L.P. (P.M. is a postdoctoral NIH fellow; J.L.F. is a postdoctoral CIBERER fellow).