Coordinate regulation of tubulin and microtubule associated protein genes during development of hamster brain

Abstract

The present study documents the patterns of mRNA expression for 5 different tubulin genes and 4 of the structural microtubule-associated protein (MAP) genes during normal development of hamster forebrain. Northern blotting in conjunction with densitometric analysis was used to study changes in the levels of the mRNAs for α I-tubulin, classes β I-, β II-, β III- and β IV-tubulin, as well as the mRNAs for tau, MAP1A, MAP1B and MAP2, using total RNA isolated from hamster forebrain at various embryonic (E) and postnatal (P) stages. Densitometric analyses of the autoradiograms from the Northern blots revealed that each of the tubulin genes exhibited distinct developmental patterns of expression, several of which appeared to be temporally correlated with the expression of specific MAP mRNAs. The β I-, β II- and β III-tubulin mRNAs increased rapidly between late embryonic stages to birth, reached peak levels early in the first postnatal week, and declined thereafter. α I-Tubulin mRNA was easily detected during embryonic stages, rose to peak levels at P7–P9 and then gradually declined. A similar pattern was seen for tau mRNA. After the first postnatal week, the size of the tau mRNA also shifted to a slightly larger size, presumably due to differential splicing. β IV-Tubulin mRNA levels did not become significant until very late in postnatal development (3–4 weeks). MAP2 mRNA expression was unusual in that peak levels were reached at two different stages of development - an initial peak occurred in the first postnatal week, followed by a decline, and then a second rise occurred during the third and fourth postnatal weeks. The expression of the β IV-tubulin mRNA coincided temporally with the second peak in MAP2 mRNA expression. MAP1B mRNA abruptly reached high levels at birth, remained abundant during the first two postnatal weeks, and then decreased. In contrast, MAP1A mRNA levels were low in the initial postnatal interval and increased only at very late developmental stages. The findings of a temporal correspondence in expression of high levels of tau and MAP1B with β I-, β II-, β III- and αI-tubulin mRNAs suggest that this profile of gene expression is one that endows greater plasticity to the neuronal cytoskeleton. Conversely, the transition to increased expression of β IV-tubulin, MAP1A, and a larger tau mRNA species defines a portion of the molecular pattern that underpins the increased stability of neuronal form during maturation.