Moving from the most recent results on Foxg1 biology, we first summarize the available information on some special pleiotropic effectors of neurodevelopmental interest, involved in controlling both transcription and post-transcriptional steps of gene expression. Then, after further analysis of the literature, we report evidence that, not strictly limited to neurodevelopmental effectors, such pleiotropy also applies to other transcription factors, involved in physiology and homeostasis. Furthermore, through the systematic analysis of a major public protein–protein interaction database, we gather strong evidence that the involvement of “canonical” transcription factors in post-transcriptional control of gene expression could be a pervasive phenomenon, characterizing hundreds of effectors. Finally, we discuss the biological significance of these findings and propose three evolutionary mechanisms that may have contributed to such an unexpected scenario.
