The study of language has involved an increasingly holistic approach, not only from psychological and breeding aspects, but also environmental and genetic aspects [3]. In our study, we can observe the result of protein interaction (Fig. 1), where the 235 genes co-expressed with ROBO1 sustain multiple interactions between them. It should be noted that the list of genes obtained from AHBA and SEEK (Fig. 1, panel A and B) resulted in few interactions of ROBO1 with other genes, perhaps these databases integrate information specific to brain tissue, in addition to biological functions and metabolic pathways related to the co-expression of our target gene in the brain are reduced to a few; even, to the fact that only a reduced number of genes that are co-expressed are introduced in the analysis. To verify the idea of specificity in the co-expression of ROBO1, it is enough to observe the data obtained from the analysis of the COXPRESdb list (Fig. 1, panel C), which is not tissue-specific and the interactions of the protein of our target gene with other proteins are is increased, since it takes into account the activity of this protein in different tissues, not only brain or nervous system tissue.
Meanwhile, the role of ROBO1 and co-expressed genes are closely related to biological processes in brain architecture: development of neuron projection, axon guidance, and neuronal migration (Table 1); in addition to the endocytosis pathway (Table 2), also related to this configuration processes in brain. It has been proven that endocytosis regulates the activity and signaling of axon guidance, mainly those that project beyond the midline of the brain [17], that is, the formation of the corpus callosum [11, 17]. The ROBO family receptors are often expressed to modulate axon guidance processes to inhibit or favor axon projection [17, 18], including in recovery processes after injury [19, 20].
The appearance of the term "negative regulation of synaptic transmission" (Table 1) could be associated with the inhibitory role on formation of connections, by preventing the connection of neurons in the required receptor through endocytosis processes [17, 18]. The terms associated with the location of cellular proteins, both in the nuclear pore and in the membrane (Table 1), are also related to ROBO family genes, were proteins encoded by these genes act repulsing neuronal projections by endocytosis [17]. Also, the term “morphogenesis of the embryonic skeletal system” (Table 1) may be associated with the role of the SLIT/ROBO signaling pathway pointed out in several studies [18, 19], which has a role in bone development and the appearance of pathologies such as osteopenia [21].
In addition, the signaling processes of the Wnt pathway, as well as the negative regulation of Wnt signaling (Table 1) appear due to the role of Wnt pathway on biological processes such as guiding axons to their target. Thus, the role of genes in this signaling pathway that support axons to cross the midline of the brain ventrally and then rotate anteriorly has been demonstrated [22], while the participation of genes from the SLIT/ROBO pathway would play a role in axon repulsion [11, 22].
Also associated with axon guidance processes, protein ubiquitination processes and the ubiquitin-dependent protein catabolic process (Table 1) refer to processes documented in animal models [23, 24], where it is eliminated the presence of proteins of the ROBO family when necessary in axonal guidance processes. These processes could well occur in humans, it will be important to also study the factors that contribute to the expression of ROBO and related genes, to measure the complexity of the formation of neural networks.