CacyBP/SIP Protein Regulates the Length and Branching of Neuronal Processes During Cortical Development

In mammals, CacyBP/SIP (calcyclin-binding protein/Siah-1-interacting protein) is widely expressed in different types of cells, including brain cells. CacyBP/SIP is involved in various cellular processes, among them proliferation, suggesting its role in tumorigenesis. In this work, we aimed to examine the role of CacyBP/SIP in cortical brain cells during developmental neurogenesis of the cerebral cortex in the opossum, Monodelphis domestica. Our results revealed that CacyBP/SIP is expressed in neurons and oligodendrocytes but not in astrocytes within the mature six-layered opossum brain. In the developing cortex of opossums at postnatal day (P) 15, we observed higher levels of CacyBP/SIP in the cortical plate, where newly generated neurons settle, compared to the subventricular neurogenic zone, where stem/progenitor cells reside. Next, we carried out experiments on primary cell cultures derived from the cerebral cortex or the anterior commissure of the opossum at two different developmental stages. We found that inhibition of CacyBP/SIP expression did not have any impact on proliferation and differentiation of cortical neurons. However, knockdown of CacyBP/SIP resulted in excessive branching of the dendritic tree and axon arbors of cortical neurons cultured from opossums at P15, which is a developmental stage corresponding to the formation of upper cortical layers. At this stage, cortical neuron axons reach the anterior commissure, that is the main fiber tract connecting the two cerebral hemispheres in marsupials, where they become myelinated by oligodendrocytes. We examined cells cultured from the anterior commissure at P35-38 during gliogenesis and observed that CacyBP/SIP did not affect the process of oligodendrogenesis or astrogenesis. Based on our results, we suggest that CacyBP/SIP is critical for arresting the branching and lengthening of dendrites and axons during formation of the cerebral cortex.