Differential Expression of Secreted Phosphoprotein 1 in the Motor Cortex among Primate Species and during Postnatal Development and Functional Recovery

Tatsuya Yamamoto,Kimika Yoshino-Saito,Akira Sato,Noriyuki Higo,Yumi Murata,Yoko Sugiyama,Shigeo Murayama,Ichiro Takashima,Tadashi Isa,Yukio Nishimura,Toshio Kojima,Takao Oishi,Izumi Sugihara

doi:10.1371/journal.pone.0065701

Abstract

We previously reported that secreted phosphoprotein 1 (SPP1) mRNA is expressed in neurons whose axons form the corticospinal tract (CST) of the rhesus macaque, but not in the corresponding neurons of the marmoset and rat. This suggests that SPP1 expression is involved in the functional or structural specialization of highly developed corticospinal systems in certain primate species. To further examine this hypothesis, we evaluated the expression of SPP1 mRNA in the motor cortex from three viewpoints: species differences, postnatal development, and functional/structural changes of the CST after a lesion of the lateral CST (l-CST) at the mid-cervical level. The density of SPP1-positive neurons in layer V of the primary motor cortex (M1) was much greater in species with highly developed corticospinal systems (i.e., rhesus macaque, capuchin monkey, and humans) than in those with less developed corticospinal systems (i.e., squirrel monkey, marmoset, and rat). SPP1-positive neurons in the macaque monkey M1 increased logarithmically in layer V during postnatal development, following a time course consistent with the increase in conduction velocity of the CST. After an l-CST lesion, SPP1-positive neurons increased in layer V of the ventral premotor cortex, in which compensatory changes in CST function/structure may occur, which positively correlated with the extent of finger dexterity recovery. These results further support the concept that the expression of SPP1 may reflect functional or structural specialization of highly developed corticospinal systems in certain primate species.

Highlights

Secreted phosphoprotein 1 (SPP1), known as osteopontin, was originally isolated from bone [1], and has been found in many cell types in other tissues including kidney tubule cells, macrophages, activated T cells, and vascular smooth muscle cells [2,3,4,5,6,7]
Similar to the results in the rhesus macaque, prominent SPP1 mRNA hybridization signals were mainly observed in layer V of capuchin M1, and weaker hybridization signals were observed in layers III and VI (Fig. 1A–C, Table 4)
Because the neuronal population with the largest cell bodies in layer V of M1 consists of corticospinal tract (CST) neurons [47,48], these results suggest that SPP1 is preferentially expressed in CST neurons of the capuchin monkey, consistent with our recent observations in the rhesus macaque [11]

Summary

Introduction

Secreted phosphoprotein 1 (SPP1), known as osteopontin, was originally isolated from bone [1], and has been found in many cell types in other tissues including kidney tubule cells, macrophages, activated T cells, and vascular smooth muscle cells [2,3,4,5,6,7]. Most of the positive neurons in the rhesus macaque M1 were presumed to be corticospinal tract (CST) neurons; SPP1 mRNA is not expressed in CST neurons of the rat and marmoset [11] Both physiological and anatomical differences in the CST exist between primates and rodents, and even between the rhesus macaque and marmoset; such differences are thought to underlie differences in finger dexterity [12,13]. For these reasons, we have suggested that the expression of SPP1 mRNA in the CST neurons of the rhesus macaque is related to the functional/structural specialization of highly developed corticospinal systems, which underlie higher levels of finger dexterity in certain primate species [11]

Methods

Results

Conclusion