Abstract
The corpus callosum (CC) is the biggest commissure that links cerebral hemispheres. Guidepost structures develop in the cortical midline during CC development and express axon guidance molecules that instruct neurons regarding the proper direction of axonal elongation toward and across the cortical midline. Neuropilin-1 (Npn1), a high affinity receptor for class 3 semaphorins (Sema3s) localized on cingulate pioneering axons, plays a crucial role in axon guidance to the midline through interactions with Sema3s. However, it remains unclear which type of Plexin is a component of Sema3 holoreceptors with Npn1 during the guidance of cingulate pioneering axons. To address the role of PlexinA1 in CC development, we examined with immunohistochemistry the localization of PlexinA1, Npn1, and Sema3s using embryonic brains from wild-type (WT) and PlexinA1-deficient (PlexinA1 knock-out (KO)) mice with a BALB/cAJ background. The immunohistochemistry confirmed the expression of PlexinA1 in callosal axons derived from the cingulate and neocortex of the WT mice on embryonic day 17.5 (E17.5) but not in the PlexinA1 KO mice. To examine the role of PlexinA1 in the navigation of callosal axons, the extension of callosal axons toward and across the midline was traced in brains of WT and PlexinA1 KO mice at E17.5. As a result, callosal axons in the PlexinA1 KO brains had a significantly lower incidence of midline crossing at E17.5 compared with the WT brains. To further examine the role of PlexinA1 in CC development, the CC phenotype was examined in PlexinA1 KO mice at postnatal day 0.5 (P0.5). Most of the PlexinA1 KO mice at P0.5 showed agenesis of the CC. These results indicate the crucial involvement of PlexinA1 in the midline crossing of callosal axons during CC development in BALB/cAJ mice.
Highlights
Neuronal interhemispheric connections and commissures composed of midline traversing axons are needed for the mammalian brain to synchronize activities between contralateral regions [1]
Together with Npn1 and L1CAM, PlexinA1 is expressed in cingulate pioneer neurons of C57BL6/J mice from embryonic day 15 (E15) to E17 [19]
The results showed that: 1) PlexinA1 was expressed in cingulate and neocortex-derived callosal axons at E17.5 during corpus callosum (CC) development; 2) the midline crossing of callosal axons was significantly impaired in PlexinA1 KO mice at E17.5 as compared with that in WT mice; and 3) agenesis of CC (AgCC) in the anterior half of CC occurred in most of the PlexinA1 KO mice at P0.5
Summary
Neuronal interhemispheric connections and commissures composed of midline traversing axons are needed for the mammalian brain to synchronize activities between contralateral regions [1]. Individuals with AgCC experience various difficulties in physical, sensory, developmental, and motor aspects that cannot be explained by the existence of conditions such as low IQ scores, neurological disorder, and impairment of the age-level communication [6]. Guidepost structures including a glial wedge, indusium griseum glia, midline zipper glia, and subcallosal sling positioned laterally, dorsally, and ventrally to the CC may provide a guidance substratum for navigating the extension of callosal axons [1, 33, 34, 35]
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