Indeed this number implies newborn Gomisin-D individuals from the latter population would suffer from this tremendous disorder, but less than 100 individuals have been diagnosed with TPI deficiency worldwide. A mutagenesis screen in mice identified four heterozygous TPI mutations that lead to a 50% reduction in catalytic TPI activity in several tissues examined. However, each homozygous or compound heterozygous offspring of these mice, which lacked any detectable phenotypical abnormalities in the heterozygote state, resulted in early embryonic lethality. These results demonstrated that mutations in the TPI gene resulting in a catalytic inactive TPI enzyme cause homozygote embryonic lethality in mice. The human population studies performed are indicating that this situation is reflected in humans as well. Consequently, the occurring mutations in TPI alleles of TPI deficiency patients cannot 
encode catalytically inactive TPI enzymes. As illustrated and demonstrated in Fig. 8, homozygote TPI null alleles are lethal, since no homozygotes carrying TPI null alleles can be detected in mouse and humans. Furthermore, TPI variants with altered dimerization properties and exhibiting almost normal specific catalytic activity like the Glu104Asp variant, occur in homozygous states causing TPI deficiency or in combination with TPI null alleles, for instance, the TPI Paris or TPI Alfortwille representing the compound heterozygote state, whereas heterozygote individuals having inherited a heterozygote null allele in combination with the wild-type allele are healthy and might have a heterozygous advantage. Regarding this issue, one should keep in mind that advantage of heterozygous state has been demonstrated for sickle cell anemia and cystic fibrosis, two other genetic disorders. Strikingly, the allelic frequency of mutations causing cystic fibrosis is comparable to the frequency of heterozygous TPI mutations in the examined Afro-American population. The fact that the yeast strain harboring the TPI variant with reduced catalytic activity is more resistant to specific oxidative stress is a first indication that mutations within TPI alleles resulting in catalytically impaired enzymes could Epimedoside-A confer an advantage to certain stress stimuli or other environmental conditions. In multicellular organisms, cells are exposed to a complex environment in which they read numerous and sometimes conflicting stimuli. Cross-communication between signaling pathways is crucial for the integration of the multiple intracellular responses elicited by simultaneous signals, allowing the generation of unique cell outputs. As a result of cross-communication, networks of signal interactions are established within the cell. The elucidation of the underlying mechanisms by which these networks are built and regulated is essential for the understanding and pharmacological treatment of pathologies in which signaling pathways are misregulated, such as some neural disorders and cancer. The Drosophila mesoderm provides an excellent system for studying signaling networks as Drosophila can be subjected to complex genetic manipulations and multiple signaling pathways are coordinately involved throughout mesoderm differentiation. After gastrulation, uncommitted mesodermal cells migrate and proliferate. Then, autonomous and non-autonomous signals pattern the mesoderm, allocating regions from which progenitors of the different mesodermal tissues, such as the somatic muscles and heart, will arise. Express the transcription factor Lethal of scute, in a process reminiscent of neural progenitor specification. These progenitors divide asymmetrically to give rise to two founder cells.