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Volume 16, Number 10, Issue of May 15, 1996 pp. 3265-3273
Copyright ©1996 Society for Neuroscience

Transgenic Expression of Embryonic MAP2 in Adult Mouse Brain: Implications for Neuronal Polarization

Received Aug. 7, 1995; revised Feb. 26, 1996; accepted Feb. 28, 1996.

Kathryn M. Marsden, Thierry Doll, Jacqueline Ferralli, Florence Botteri, and Andrew Matus

Friedrich Miescher Institute, Basel, 4002 Switzerland

The major neuronal microtubule-associated protein MAP2 is selectively localized in dendrites, where its expression is under strong developmental regulation. To learn more about its potential effects on neuronal morphogenesis and its sorting within the neuronal cytoplasm, we have raised transgenic mice that express high levels of the embryonic form, MAP2c, in the adult brain. One transgenic line expressed higher levels of MAP2c than endogenous adult MAP2. This had no detectable effect on either the arrangement or morphology of neurons, suggesting that although MAP2c is necessary for neuronal morphogenesis it is not involved in its regulation. Like endogenous adult MAP2, transgenic MAP2c was present in dendrites but not axons, indicating that the signal responsible for its cytoplasmic sorting is contained within the 1.5 kb of its coding sequence. In situ hybridization with specific probes showed that transgenic MAP2c mRNA was limited to cell bodies. Thus, the dendritic localization of MAP2c protein cannot be the result of previous transport of its mRNA but must depend on a signal associated with the protein itself. Furthermore, because the amino acid sequence of MAP2c is present in all forms of MAP2, this signal is also contained within adult high-M_r MAP2 protein. This raises the possibility that, rather than the conventional scheme of mRNA sorting preceding protein localization, the transport of adult MAP2 mRNA into dendrites could depend on it being part of a translation complex in which the targeting signal is on the nascent protein.

Key words: neuronal differentiation; dendrites; cytoskeleton; polarization; transgenic; microtubules; morphogenesis; development; brain; nervous system; mouse

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