The trigeminal ganglia are responsible for sensory processing in the face, oral and nasal cavities. Injuries and malformations of this nerve are clinically and cosmetically devastating to humans. Two different tissues contribute to the formation of the trigeminal ganglia: the ectodermal placode and the cranial neural crest. Most mechanoceptive neurons (trkC+ and trkB+) are derived from the placode, whereas the neural crest gives rise to all of the nociceptive and thermoceptive neurons (trkA+). The broad objectives of this research are to understand how these distinct classes of sensory neurons develop and how they innervate to the locales within the face. In preliminary studies, my colleagues and I have found that a single neural determination gene, Neurogenin1 (ngnl), is required to direct formation of the entire trigeminal ganglion. Research described in this proposal is primarily based on this finding. We will address three fundamental questions: 1) how is the neural crest-derived neurogenesis regulated by extrinsic signals from the pioneer placodal neurons? 2) How are axons of crest-derived neurons projected to precise locales within the face? 3) What are the intrinsic molecular mechanisms by which sensory sublineages are specified? For the first question, we will determine if the potential of the trigeminal neural crest cells to form the trkB+ and trkC+ neurons is restricted by pioneer placodal neurons. We will also determine if specification of other neuronal features is dependent on this cell-to-cell interaction as well. To do this, we will create trigeminal crest ganglia that completely lack the pioneer placodal neurons, and then to examine how the remained crest-derived neurogenesis will be affected. For the second question, a testable hypothesis is suggested by the classic experiments of Victor Hamburger. Pioneer placode-derived neurons may play an essential role for axon pathfinding of the crest-derived neurons. This hypothesis will be tested by examining axonal projections of crest-derived neurons that develop in mice without placodal neurons. For the third question, we will use """"""""Gene Family Differential Screening,"""""""" a procedure developed by the investigator, to isolate regulatory molecules that are expressed in a subset of sensory neurons. These sublineage-specific genes will be candidate molecules that control cell subtype specification.
