Differential localization of high- and low-molecular-weight variants of microtubule-associated protein 2 in the...

Microtubule-associated protein 2 (MAP2) occurs in developing mammalian neuronal tissue as both high- and low-molecular-weight forms with temporally regulated expression. We studied the MAP2 expression in the developing rat telencephalon with monoclonal antibodies that recognized both the high- and low-molecular-weight forms of MAP2 variants or that specifically recognized high-molecular-weight forms of MAP2 variants. Differences in the staining patterns of these antibodies reflected differences in the distribution of the high- and low-molecular-weight MAP2s. The immunoreactive sites of high- and low-molecular-weight MAP2 had a more widespread distribution in the embryonic telencephalon than those of high-molecular-weight MAP2. Many bipolar cells in the ganglionic eminence (GE) and in the intermediate zone (IZ) of the neocortex showed low-molecular-weight MAP2 immunoreactivity, but they showed weak or no high-molecular-weight MAP2 immunoreactivity. Expression of mRNA containing exons common to high- and low-molecular-weight MAP2 was detected in the tangentially ellipsoidal cells in the IZ, but expression of mRNA containing an exon specific to high-molecular-weight MAP2 was not detected in these cells by in situ hybridization. We interpreted these observations as indicating that the bipolar cells contained MAP2c preferentially, but contained MAP2a and MAP2b (MAP2a/b) at a very low or negligible level. The cells that expressed MAP2c preferentially among the MAP2 splicing variants composed 50% of the preplate cells, most of the MAP2-positive cells in the hippocampus and the corpus callosum. Double labeling by DiI staining and Dlx2 immunohistochemistry, or by Dlx2 and MAP2 immunohistochemistry, revealed that most of the Dlx2-positive cells in the IZ expressed MAP2c preferentially at embryonic day 16. Another double-labeling study revealed that most GAD-positive cells in the preplate were MAP2a/b positive, whereas most GAD-positive cells in the IZ expressed MAP2c preferentially, with only a negligible level of MAP2a/b immunoreactivity. We conclude that MAP2 immunoreactivity in the IZ was localized in the tangentially migrating neurons. The tangentially migrating neurons seemed to acquire MAP2a/b immunoreactivity as they entered the preplate or cortical plate and developed into mature neurons. Radially migrating neurons in the IZ were MAP2 negative. After entering to the preplate or the cortical plate, they became MAP2a/b positive as they developed into mature neurons.