Neural Crest and Placodal Cells Contributions to Cranial Sensory Development

The sensory system of vertebrates is incredibly complex. Many important components of the sensory system are located within the cranial region, including the sense organs and cranial sensory ganglia. Early in development two progenitor populations, the neural crest and the cranial placodes, arise at the neural plate border and throughout vertebrate development contribute to the developing vertebrate peripheral sensory system. The interactions and contributions of both of these cell populations to the development of the pituitary system, the eyes, the nose, the ears, and the cranial ganglia of the head and neck are vital for the appropriate development of an embryo’s nervous system. In this dissertation we explore the contributions of both the neural crest and placodal cells to the sensory system of the developing embryo. In Chapter 1 we review the origin of these two cell populations at the neural plate border and give an overview of the development of the various cranial peripheral sensory systems and their placode and neural crest contributions. In Chapter 2 we use replication incompetent avian retroviruses to lineage trace both the olfactory placode and the neural crest to their respective cellular contributions in the olfactory system. We confirm previous studies which showed that GnRH neurons of the nose receive contributions from both the olfactory placode and the neural crest and we show that both the olfactory placode and the neural crest contribute to the olfactory neurons of the olfactory epithelium. However, neural crest alone gives rise to the olfactory ensheathing cells which are critical for neuronal migration from the olfactory epithelium to the forebrain. We also show for the first time that the neural crest gives rise to the p63 positive horizontal basal stem cell population of the olfactory epithelium. In Chapter 3, along with collaborators from SUNY Buffalo, we show that multipotent and functional NC cells can be derived by induction with a growth factor cocktail containing FGF2 and IGF1 from cultures of human inter-follicular keratinocytes (KC) isolated from elderly donors. They also maintained their multipotency, as evidenced by their ability to differentiate into all NC-specific lineages including neurons, Schwann cells, melanocytes, and smooth muscle cells (SMC). Notably, upon implantation into chick embryos, adult NC cells behaved similar to their embryonic counterparts, migrated along stereotypical pathways, and contributed to multiple NC derivatives in ovo. These results suggest that KC-derived NC cells may provide an easily accessible, autologous source of stem cells that can be used for treatment of neurodegenerative diseases or as a model system for studying disease pathophysiology and drug development. Finally, in Chapter 4 we discuss future directions and experiments that I plan to pursue post-graduation. I propose to conduct a closer examination of the variants of GnRH neurons across developmental time in various representative taxa of cartilaginous fish and reptiles. Furthermore, I intend to identify and experimentally confirm a molecular regulatory region for GnRH2, the most highly conserved variant across vertebrates, within the chicken embryo. Once this regulatory region is identified, the sequence can also be used to probe the genomes of other non-model taxa. Finally, I would like to perform lineage analysis using DiI in a non-model system to probe the embryonic origins (neural crest vs. placode) of the GnRH neurons in more ancient taxa.