Embryonic origin of the olfactory sensory system: Fate map, lineage analysis and specification of the avian olfactory placode.

摘要

Coordinating the precise spatiotemporal arrangement of diverse cell types within the developing nervous system is an intricate, yet robust process. Cranial placodes are bilaterally paired ectodermal thickenings that are present in stereotypic positions in the embryonic head and differentiate into sensory organs and cranial ganglia. For example, derivatives of the olfactory placode are responsible for our perception of smell. Based on fate-maps constructed by dye-labeling small populations of cells in early chick embryos, we find that olfactory precursors are spread over a broad domain at head-fold stages and intermingle with lens, epidermal and neural precursors. However, tracing the lineage of single cells in this domain surprisingly suggests that lens and nasal precursors are already specified with respect to their fate. Confocal time-lapse analysis confirmed the segregation of these precursors at ∼stage 8 at which time Pax6 and Dlx5 are differentially upregulated in lens and nasal precursors, respectively. This possibly indicates that cell sorting is motivated by differences in precursor fate.; To understand how and when the nasal placode is induced, I have performed transplantation experiments to define the extent of competence and commitment within the ectoderm to form the nasal placode. Initially, all levels of ectoderm are capable of expressing PAX6 and DLX3 (markers of the olfactory placode) when grafted to the olfactory domain; hindbrain and trunk level ectoderm lose this competence rapidly by stage 10, suggesting that inducing signals are localized to anterior regions before this stage and/or that later signals refine the olfactory placode-forming region. Irreversible commitment towards an olfactory fate occurs concomitant with the morphological appearance of the placode at stage 14. Isolated presumptive olfactory placode ectoderm is specified to express PAX6 and DLX3 between stages 8-10; however, neuronal specification begins later, around stage 14. This implies that signals direct olfactory placode fate before it is morphologically visible; an inference, which is corroborated by results obtained from lineage analysis. The next step is to determine the molecular nature of the inducing signals. Embryological manipulations in combination with fate-mapping and lineage studies offer important insights into the mechanisms by which sensory systems are assembled during development.