Expression pattern of integrin ?1 subunit in purkinje cells of rat and cerebellar mutant mice

Abstract

We found that integrin beta 1 subunit (INT beta 1)-immunoreactive Purkinje cells first appeared caudally at postnatal day (PD) 6 of rat and most Purkinje cells gradually became positive by PD 12. The expression of INT beta 1 was then suppressed in some of these cells, so that the positive Purkinje cells in the adult were organized into parasagittal bands interposed by negative cells throughout the vermis and hemispheres. When Purkinje cells were deprived of their climbing fiber innervation by inferior cerebellar pedunculotomy or by transplantation of cerebellar anlagen into the anterior eye chamber, the subsequent patterning of INT beta 1-positive Purkinje cells was not changed. In both reeler and weaver mice, the INT beta 1-positive parasagittal bands were observed, however, the Purkinje cells in the staggerer mice did not express INT beta 1 at any stage. These data suggest that the expression of INT beta 1 in Purkinje cells is genetically programmed in the developing cerebellum, and that the afferent synaptic inputs by climbing and parallel fibers are not prerequisites for INT beta 1 expression in Purkinje cells. Therefore, the unique distribution patterns of INT beta 1-positive Purkinje cells provides a new marker for postnatal development of rodent cerebella.

Integrins in the development function and dysfunction of the nervous system

“…Alternatively, or in combination, signal transduction events mediated by integrins might lead to altered cytoskeletal or membrane topology that strengthens the synapse. Along these lines, Murase and Hayashi have reported that expression of the integrin beta-1 subunit is increased by seizure activity, indicating that activity may alter synapses by altering integrin levels (124). Integrins can give rise to calcium influx (e.g.…”

“…In the central nervous system, integrins of the beta-1 family appear to be widely expressed not only in developing neurons and glia, but also in the adult (45,124,125). A survey of integrin mRNA localization in adult brain by in situ hybridization detected mRNAs encoding alpha-1, alpha-3, alpha-4, alpha-5, alpha-6, alpha-7, alpha-8, alpha-v, beta-1, beta-4, and beta-5 in both neurons and glia in various brain regions (125).…”

“…For example, alpha-4 mRNA was detected only in discrete regions of the limbic forebrain. Integrin protein immunoreactivity has also been detected in brain for the alpha-1, alpha-3, alpha-5, alpha-8, alpha-v, beta-1, beta-3, beta-5 and beta-8 subunits (45, 124,[127][128][129][130][131][132][133][134][135]. In some cases, integrin subunit protein staining is seen in regions where the mRNA is not detected ( e.g., alpha-8, (132)), indicating that distribution may be wider than revealed by in situ hybridization.…”

Integrin ?1 localization in murine central and peripheral nervous system

“…Purkinje cells were expected to express INT␣1, because they express integrin ␤1 subunit (Murase and Hayashi, 1996), which is capable of forming a functional heterodimer with INT␣1, and also because they were found to be catecholaminergic neurons (Takada et al, 1993;Fujii et al, 1994;Sakai et al, 1995;Nelson et al, 1997) in addition to their GABAergic function (Ito and Yoshida, 1964;Obata and Takeda, 1969;Curtis et al, 1970;Fonnum et al, 1970;McLaughlin et al, 1974;Ito, 1984). We confirmed the TH-immunoreactivity of Purkinje cells in this study, but did not observe INT␣1 expression in these cells.…”

“…In addition, we found that integrin ␣v␤5 heterodimer is expressed in growing parallel fibers of postnatal cerebellum (Murase and Hayashi, submitted), and also that a subset of adult Purkinje cells express integrin ␤1 subunit (Murase and Hayashi, 1996). These findings encouraged us to examine the expression of various types of integrins in the central nervous system.…”