Aminergic control of early devlopment

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The functions of the neurotransmitter serotonin (5-HT, 5-hydroxytryptamine) are intensively studied and well known in the central nervous system and some other tissues.  The presence of 5-HT and its receptors in female reproductive tissues has been sporadically reported in vertebrate animals but it is in some invertebrates that precise functions of 5-HT in reproduction have been better described, in particular in molluscan species such as surf clam.  In this species, 5-HT triggers spawning in mature animals, and induces oocyte meiotic maturation when added to isolated oocytes, thus mimicking a process of activation normally set by the fertilizing sperm.  Using surf clam as a model, we have previously shown that their prophase I-arrested oocytes possess a 5-HT receptor whose activation triggers increased intracellular calcium and cAMP, and leads to full meiotic maturation.  Our specific objectives will be to further characterize a cloned putative clam oocyte 5-HT receptor by studying its signalling properties and pharmacological profile when transfected in mammalian host cells (HEK-293), and determine whether it is the specific receptor leading to meiotic maturation.   Other aminergic receptors expressed in clam oocytes will be investigated, including a cloned putative octopamine receptor, and tested for their capacity to influence meiotic maturation.  We will also verify to what extent observed cAMP rises elicited by 5-HT are causal in reinitiating meiosis in quiescent oocytes.  We will examine the capacity of specific activators and inhibitors of protein kinase A to alter meiosis reinitiation by 5-HT and establish possible links between internal cAMP levels and the MAPK signaling pathway relative to intracellular calcium rises.  Finally, the possible involvement of other biogenic amines such as octopamine and dopamine in the regulation of reproduction will be examined.  Our research program will clarify the mechanisms by which aminergic receptors are involved in reproductive and early developmental processes.  Our work will pave the way for understanding potential roles of a growing list of aminergic receptors of unknown local function but reported to be expressed in reproductive cells of not only invertebrate but vertebrate species, as well.