Abstract
The corpus callosum forms the major interhemispheric connection in the human brain and is unique to eutherian (or placental) mammals. The developmental events associated with the evolutionary emergence of this structure, however, remain poorly understood. A key step in callosal formation is the prior remodeling of the interhemispheric fissure by embryonic astroglial cells, which then subsequently act as a permissive substrate for callosal axons, enabling them to cross the interhemispheric midline. However, whether astroglial-mediated interhemispheric remodeling is unique to eutherian mammals, and thus possibly associated with the phylogenetic origin of the corpus callosum, or instead is a general feature of mammalian brain development, is not yet known. To investigate this, we performed a comparative analysis of interhemispheric remodeling in eutherian and non-eutherian mammals, whose lineages branched off before the evolution of the corpus callosum. Whole brain MRI analyses revealed that the interhemispheric fissure is retained into adulthood in marsupials and monotremes, in contrast to eutherians (mice), in which the fissure is significantly remodeled throughout development. Histological analyses further demonstrated that, while midline astroglia are present in developing marsupials, these cells do not intercalate with one another through the intervening interhemispheric fissure, as they do in developing mice. Thus, developing marsupials do not undergo astroglial-mediated interhemispheric remodeling. As remodeling of the interhemispheric fissure is essential for the subsequent formation of the corpus callosum in eutherians, our data highlight the role of astroglial-mediated interhemispheric remodeling in the evolutionary origin of the corpus callosum.
Highlights
Interhemispheric brain connections are crucial for the integration of neural processes between the left and right cerebral hemispheres
As astroglial-mediated interhemispheric remodeling is a developmental process that is critical for the formation of the corpus callosum, we asked whether this cellular process is exclusive to eutherian mammals, and associated with the phylogenetic origin of the corpus callosum, or instead is a more general mammalian process that can be observed in non-eutherian species
Structural T1-weighted MRI images of the interhemispheric midline from fixed brains of adult mice (Mus musculus, Placentalia; Fig. 1a) were compared with equivalent images obtained from fixed brains of adult fat-tailed dunnarts (Sminthopsis crassicaudata, Marsupialia, Fig. 1b) and platypus (Ornithorhynchus anatinus, Monotremata; Fig. 1c)
Summary
Interhemispheric brain connections are crucial for the integration of neural processes between the left and right cerebral hemispheres. The corpus callosum forms the major interhemispheric connection. We demonstrated that prior remodeling of the IHF by specialized astroglial cells is essential for callosal tract formation, and that aberrant retention of the IHF due to defects in this process results in agenesis (or absence) of the corpus callosum in both mice and humans [8]. Interhemispheric remodeling is initiated by the transition of these specialized glial cells (known as midline zipper glia; MZG) from radial glia into multipolar astroglia. This transition into a multipolar state is required for MZG cells to intercalate with one another across the IHF and degrade the intervening leptomeninges. As astroglial-mediated interhemispheric remodeling is a developmental process that is critical for the formation of the corpus callosum, we asked whether this cellular process is exclusive to eutherian mammals, and associated with the phylogenetic origin of the corpus callosum, or instead is a more general mammalian process that can be observed in non-eutherian species
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
