DEVELOPMENT OF THE OLFACTORY SYSTEM

The normal processes of neural development in the central
nervous system (CNS) depend upon precisely-timed expression of
various cellular and molecular factors. Delayed or precocial onset
of these factors can affect the outcome of cell origin, migration,
axonal and dendritic outgrowth, synaptogenesis, and cell death in a
number of brain regions. The consequences can be devastating to
normal neural function. The thrust of this proposal is to study, in
detail, a brain region critically dependent upon timely
development of afferent innervation for its growth and
maturation. In the African clawed frog, Xenopus laevis, we will
examine the development of the olfactory bulb in the normal
embryo, in animals deafferented early in development, and in
animals receiving augmented afferentation during embryonic
development. Experimental manipulations to be used are (1)
removal of the olfactory placode before receptor axons contact
the olfactory bulb, (2) removal of the placode after some axons
penetrate and stimulate some differentiation of the bulb, and (3)
transplantation of an extra placode to the rostral cranium of
normal embryos. By comparing the development of the olfactory
bulbs in normal animals to that of the bulbs from the
experimentally manipulated embryos, we hope to identify those
cellular factors induced or influenced by the olfactory axons
during development. These comparisons will be made with a
variety of experimental methods. 3H-thymidine autoradiography
will be used to study the time of origin of neurons in the olfactory
bulb and determine the number of neurons generated at each
stage. Neurons will be counted at various stages to see if cell
death normally occurs in the bulb and whether this process is
affected by the experimental manipulations. Golgi impregnation
studies will serve to examine dendritic development in the mitral
cells, which are the major output cells of the bulb. With
immunocytochemistry, we will study onset of neurotransmitter
expression, and with electron microscopy, synaptogenesis in the
glomerular and external plexiform layers. All studies will include
quantitative analyses. The underlying purpose of my work is to
understand the cellular and molecular factors that control the
development of sensory systems, with a hope of preventing or
alleviating problems associated with CNS birth defects and
disorders.