Specific tumor-associated rearrangements involving the regions 11p13 and 11p15 have been extensively documented. However, cytogenetic definition of the breakpoints occurring at the boundaries of these two regions was not precise enough to correlate with the molecular data. Using probes corresponding to the genes coding for MYOD1, CTSD, LDHA, and RBTN1 and to the anonymous sequence D11S776, we have reassessed the breakpoints of three hybrids (J1.10, BID7, and NYX3.1) and confirmed the localization or more precisely mapped these four genes and the anonymous DNA marker on different subregions of 11pter→p13, including the smallest region of 1 lpl 5.5 duplicated in a patient with Beckwith-Wiedemann syndrome.

Krü ppel (Kr) is a segmentation gene which plays one of the key morphogenetic roles in early development of Drosophila. In order to better elucidate the regulatory role of this gene, we analyzed quantitative expression patterns of other segmentation genes in homozygous Kr mutants. During cleavage cycle 14A the posterior domain of giant (gt) and even-skipped (eve) stripe 7 are significantly shifted to the anterior relative to their position in wild-type embryos. We did not detect this difference in positions until 13 and 26 min from the beginning of cycle 14A for gt posterior domain and eve stripe 7, respectively. During the latter part of cycle 14A, these domains shift by 12 and 5% embryo length as compared with wild-type. As zygotic gap proteins first appear at cleavage cycle 12, our results point on the existence of a significant delay in the influence of absence of Kr protein on the behavior of gene expression domains. This suggests that zygotic gap-gap cross-regulation does not play a role in the positioning of segmentation gene expression domains at early times and comes into effect only in cycle 14A. Moreover, we have detected that by the end of cycle 14A in Kr mutants gt posterior domain shifts to the position of neighbouring knirps (kni) domain and does not move further to the anterior, so that none of the genes occupies the position of missing Kr. We propose that in Kr mutants the positions of posterior domains of gt and kni are set by hunchback (hb) which functions as a strong repressor. We have used the chicken embryo and a novel Systems approach to generate a preliminary network model of the inductive signals and their downstream targets during cardiogenesis. Data was combined from three complementary microarray studies. First we investigated the combinatorial contributions of Bmp and Fgf signaling to gene expression in cardiogenic mesoderm. HH stage 4 embryos were exposed to the FgfR inhibitor SU5402, or the Smad1, 5, 8 inhibitor Dorsomorphin, or both molecules, and cultured until HH stage 7. Precardiac mesoderm was microdissected from treated and control embryos and RNA isolated for comparative microarray analysis. A custom long oligo microarray was used with a novel analysis approach that allows for the dissection of individual and combinatorial contributions of each signaling pathway to the expression of each gene. Of the 27 possible regulatory categories only about half are used during cardiogenesis. Remarkably, mapping these positive and negative Bmp/Fgf regulatory categories in relation to Bmp and Fgf expression patterns provides a mechanism to define the distribution of gene expression across the primary and secondary heart fields. Next, we identified the temporal changes in global gene expression that occur from the initial appearance of mesoderm during gastrulation to onset of cardiac myocyte differentiation. Finally, we determined the changes in gene expression that occur when cardiogenesis is induced in explanted posterior mesoderm by exposure to Bmp2 and Fgf4. Information from these exper...