One such morphogen is serotonin a neurotransmitter selleck chemicals Erlotinib of clinical relevance that has interesting roles outside the central nervous system. In two vertebrate species, serotonergic signaling has been shown to be required for LR patterning. In the frog embryo, it is known that 5HT accumulates in the right blastomeres in a rapid process dependent on asymmetric voltage gradients across the midline and the presence of open gap junc tions through which it traverses. In Xenopus embryos, many aspects of this system have been elucidated the source of the electrophoretic force driving this 5HT gradient has been molecularly charac terized, and indeed many aspects are known in enough quantitative detail to allow the whole system to be computationally modeled.

However, one fundamental question has not been addressed how does this physiological gradient, occurring in the frog at a time when the zygotic genome is mostly quiescent, cou ple to the later transcriptional cascade of asymmetrically expressed genes that is known to control organ posi tioning Specifically how does the arrival of 5HT within the right side blastomeres control gene expression Well known 5HT receptor families are not ideal candidates because they are functional on the outside surface of the plasma membrane, while the 5HT arrives through gap junctions, and thus requires an intracellular binding target. To better understand how intracellular 5HT signaling is transduced into stable gene expression, from early to very late developmental stages, we hypothesized the involvement of epigenetic machinery as a new compo nent of the LR establishment.

Such a mechanism is attractive because once epigenetic markers are deposited on the chromatin, they remain stable along successive cell divisions carrying the epigenetic signature of an activated or repressed state of the chromatin. More spe cifically, we sought to determine whether early manipu lation of the epigenetic state of the embryo would affect LR relevant genes expressed at late developmental stages. Changes in the state of the chromatin have a key role for the proper control of gene expression during devel opment. Post translational modifications such as lysine acetylation constitute a code allowing specific interac tions between chromatin and DNA binding proteins that ultimately will dictate the status of activation of a gene. These modifications take place at the chro matin level and involve the acetylation of lysines in the amino terminal tail of core histones. HDACs are important players for epigenetic memory control as they act by decreasing the levels of acetylated histones leading to chromatin compaction Entinostat and repres sion.