Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization

Abstract

MAP1B and MAP2 are major members of neuronal microtubule-associated proteins (MAPs). To gain insights into the function of MAP2 in vivo, we generated MAP2-deficient (map2−/−) mice. They developed without any apparent abnormalities, which indicates that MAP2 is dispensable in mouse survival. Because previous reports suggest a functional redundancy among MAPs, we next generated mice lacking both MAP2 and MAP1B to test their possible synergistic functions in vivo. Map2 − /−map1b −/− mice died in their perinatal period. They showed not only fiber tract malformations but also disrupted cortical patterning caused by retarded neuronal migration. In spite of this, their cortical layer maintained an “inside-out” pattern. Detailed observation of primary cultures of hippocampal neurons from map2 −/−map1b −/− mice revealed inhibited microtubule bundling and neurite elongation. In these neurons, synergistic effects caused by the loss of MAP2 and MAP1B were more apparent in dendrites than in axons. The spacing of microtubules was reduced significantly in map2 −/−map1b −/− mice in vitro and in vivo. These results suggest that MAP2 and MAP1B have overlapping functions in neuronal migration and neurite outgrowth by organizing microtubules in developing neurons both for axonal and dendritic morphogenesis but more dominantly for dendritic morphogenesis.

Actin Aggregations Mark the Sites of Neurite Initiation

“…Consistently, antisense depletion of MAP2 inhibited neurite initiation [35]. However, other work showed that contact-induced neurite formation in sympathetic neurons still took place in the presence of microtubule stabilizing/destabilizing pharmacological agents [36], and that neurite initiation still occurred in mice double knockout for MAP2 and MAP1B [37], suggesting alterative/redundant mechanisms for neurite initiation. Based on the ability of MAPs to interact with actin, coordination between the two cytoskeletal structures has been proposed to mediate neurite initiation [38,39].…”

Collapsin Response Mediator Protein 1 Mediates Reelin Signaling in Cortical Neuronal Migration

“…Slides were analyzed using Olympus (Tokyo, Japan) IX-71 microscopy using a 10ϫ objective. For quantitative measurements, comparable sections were chosen at the somatosensory cortex, which was divided into 10 horizontal bins from the superficial to the deep, and labeled nuclei in each bin were counted (Teng et al, 2001).…”

Generation of noncentrosomal microtubule arrays

“…Tau, which is preferentially found in axons (Binder et al, 1985), and MAP2, which is preferentially found in dendrites (Bernhardt and Matus, 1984), might bundle MTs because overexpression of these proteins in insect cells generates processes that have MT-MT spacings that reflect the size of the MAP (Chen et al, 1992). Nonetheless, mice lacking either tau or MAP2 have relatively normal neurons, which suggests that other factors are involved (Harada et al, 1994;Teng et al, 2001). Motor proteins, which help bundle MTs in S. pombe and plant cells, are other likely candidates.…”