Expression of type 1 inositol 1,4,5-trisphosphate receptor during axogenesis and synaptic contact in the central and peripheral nervous system of developing rat

Abstract

Release of intracellular Ca2+ is triggered by the second messenger inositol 1,4,5-trisphosphate, which binds to the inositol 1,4,5-trisphosphate receptor and gates the opening of an intrinsic calcium channel in the endoplasmic reticulum. In order to understand the importance of this mechanism in development, we have examined the distribution of the type 1 inositol 1,4,5-trisphosphate receptor during development, in some areas of the rat brain and spinal cord and in peripheral neurons, using in situ hybridization and immunohistochemistry. In brain, we find that type 1 inositol 1,4,5-trisphosphate receptor is expressed in neurons from very early in development; low levels of expression are first detected after the neurons have migrated to their final positions, when they start to differentiate and begin axonal growth. Increasing levels of expression are observed later in development, during the time of synaptogenesis and dendritic contact. Glial cells do not express type 1 inositol 1,4,5-trisphosphate receptor, except for a transient period of expression, probably by oligodendrocytes, in developing fibre tracts during the onset of myelination. In contrast with the brain, both grey and white matter of the spinal cord express type 1 inositol 1,4,5-trisphosphate receptor throughout development, and it remains present in the adult spinal cord. We also show, for the first time, that type 1 inositol 1,4,5-trisphosphate receptor is expressed in the peripheral nervous system. Strong labelling was observed in the dorsal root ganglia and during development this expression seems to coincide with the onset of axogenesis. These results suggest that type 1 inositol 1,4,5-trisphosphate may be involved in the regulatory mechanism controlling Ca2+ levels in neurons during the periods of cell differentiation, axogenesis and synaptogenesis.