Complementary expression of EphA7 and SCO-spondin during posterior commissure development

Abstract

Bilaterally symmetric organisms need to exchange information between the two sides of their bodies in order to integrate sensory inputs and coordinate motor control. This exchange occurs through commissures formed by neurons that project axons across the midline to the contralateral side of the central nervous system. The posterior commissure is the first transversal axonal tract of the embryonic vertebrate brain. It is located in the dorsal portion of the prosomere 1, at the caudal diencephalon. The axons of the posterior commissure principally come from neurons of ventrolateral and dorsolateral pretectal nuclei (parvocellular and magnocellular nucleus of the posterior commissure, respectively) that extend their axons toward the dorsal region. The trajectory of these axons can be divided into the following three stages: (1) dorsal axon extension towards the lateral roof plate; (2) fasciculation in the lateral roof plate; and (3) midline decision of turning to the ipsilateral side or continuing to the opposite side. The mechanisms and molecules that guide the axons during these steps are unknown. In the present work, immunohistochemical and in situ hybridization analyses were performed, with results suggesting the participation of EphA7 in guiding axons from the ventral to the dorsal region of the prosomere 1 through the generation of an axonal corridor limited by repulsive EphA7 walls. At the lateral roof plate, the axons became fasciculated in presence of SCO-spondin until reaching the midline. Finally, EphA7 expression was observed in the diencephalic midline roof plate, specifically in the region where some axons turn to the ipsilateral side, suggesting its participation in this decision. In summary, the present work proposes a mechanism of posterior commissure formation orchestrated by the complementary expression of the axon guidance cues SCO-spondin and EphA7.

Expression Patterns of Extracellular Matrix Proteins during Posterior Commissure Development

“…First, the axons run dorsally toward the lateral roof plate. In this step, studies performed in chick embryos revealed that axons are surrounded by EphA7-expressing cells that appear to form a repulsion barrier that delimits the axonal trajectory (Stanic et al, 2014 ). Second, in the lateral roof plate the presence of SCO-spondin and slit2 in chick and Xenopus leavis embryos respectively promote fasciculation and drive the axons to the midline (Stanic et al, 2010 ; Tosa et al, 2015 ).…”

“…Finally, at the midline, axons either turn to the ipsilateral side or continue to the opposite side. Worth noting, a set of EphA7-expressing cells at the midline seems critical in the axonal decision process (Stanic et al, 2014 ). The relevance of the caudal diencephalic roof plate in guiding the PC axons is also sustained by data from various null mutant mice (mutant for pax2/5, pax6, msx 1 ), which display a wide range of abnormalities in the diencephalic roof plate and fail to form a normal PC (Schwarz et al, 1999 ; Louvi and Wassef, 2000 ; Estivill-Torrus et al, 2001 ; Fernandez-Llebrez et al, 2004 ; Ramos et al, 2004 ).…”

Effect of EphA7 Silencing on Proliferation, Invasion and Apoptosis in Human Laryngeal Cancer Cell Lines Hep-2 and AMC-HN-8

“…EphA7 is widely expressed in embryonic tissues, especially developing central nervous system [18]. A previous study disclosed that the EphA7 receptor regulates apoptosis during early brain development.…”

Involvement of Slit–Robo signaling in the development of the posterior commissure and concomitant swimming behavior in Xenopus laevis

“…However, abnormality in the PC has not been reported in other amniotes including slit or robo mutant mice [ 27 , 28 , 30 ]. It may be due to the fact that the disruption of slit or robo signaling may be compensated for by other paralogues or guidance molecules, such as the EphA7-dependent system which is involved in the formation of the chick PC [ 55 ]. Thus, further functional studies using vertebrate groups should be necessary to identify the evolutionary process of PC formation.…”

“…Although it is unknown whether there is a direct link between the PC and swimming behavior, it is important to note that axons in the PC stem from several types of neurons. Previous studies have shown that the PC contains axons that stem from several nuclei, including the nTPC [ 46 , 55 ]. In mammals, the PC is involved in oculomotor movement by transmitting visual information coming from the cerebral cortex (visual area) and superior colliculus [ 56 , 57 ].…”