Genetic mechanisms controlling anterior expansion of the central nervous system

In bilaterally-symmetric animals (Bilateria), condensation of neurons and ganglia into a centralized nervous system (CNS) constitutes a salient feature. In most, if not all, Bilateria another prominent aspect is that the anterior regions of the CNS are typically larger than the posterior ones. Detailed studies in Drosophila melanogaster (Drosophila) have revealed that anterior expansion in this species stems from three major developmental features: the generation of more progenitors anteriorly, an extended phase of proliferation of anterior progenitors, and more proliferative daughter cells in anterior regions. These brain-specific features combine to generate a larger average lineage size and higher cell numbers in the brain, when compared to more posterior regions. Genetic studies reveal that these anterior-posterior (A-P) differences are controlled by the modulation of temporal programs, common to all progenitors, as well as by Hox homeotic genes, expressed in the nerve cord, and brain-specific factors. All of these regulatory features are gated by the action of the PRC2 epigenetic complex. Studies in mammals indicate that most, if not all of these anterior expansion principles and the underlying genetic programs are evolutionarily conserved. These findings further lend support for the recently proposed idea that the brain and nerve cord may have originated from different parts of the nervous system present in the Bilaterian ancestor. This brain-nerve cord "fusion" concept may help explain a number of the well-known fundamental differences in the biology of the brain, when compared to the nerve cord.