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During the regeneration of freshwater planarians, polarity and patterning programs play essential roles in determining whether a head or a tail regenerates at anterior or posterior-facing wounds. This decision is made very soon after amputation. The pivotal role of the Wnt/β-catenin and Hh signaling pathways in re-establishing anterior-posterior (AP) polarity has been well documented. However, the mechanisms that control the growth and differentiation of the blastema in accordance with its AP identity are less well understood. Previous studies have described a role of Smed-egfr-3, a planarian epidermal growth factor receptor, in blastema growth and differentiation. Here, we identify Smed-egr-4, a zinc-finger transcription factor belonging to the early growth response gene family, as a putative downstream target of Smed-egfr-3. Smed-egr-4 is mainly expressed in the central nervous system and its silencing inhibits anterior regeneration without affecting the regeneration of posterior regions. Single and combinatorial RNA interference to target different elements of the Wnt/β-catenin pathway, together with expression analysis of brain- and anterior-specific markers, revealed that Smed-egr-4: (1) is expressed in two phases - an early Smed-egfr-3-independent phase and a late Smed-egfr-3-dependent phase; (2) is necessary for the differentiation of the brain primordia in the early stages of regeneration; and (3) that it appears to antagonize the activity of the Wnt/β-catenin pathway to allow head regeneration. These results suggest that a conserved EGFR/egr pathway plays an important role in cell differentiation during planarian regeneration and indicate an association between early brain differentiation and the proper progression of head regeneration. [ABSTRACT FROM AUTHOR]

Freshwater planarians are unique in their ability to regenerate a complete Central Nervous System (CNS) from almost any small piece of their body in just a few days. The planarian CNS contains a pair of anterior cephalic ganglia lying on top of two ventral nerve cords that extend along the length of the animal. Studies of planarian CNS regeneration have generally used pan-neural markers, which provide only a general overview of the process. Nevertheless, some reports have started to characterize the genes that are required for this process. In this study, to obtain a more detailed description of planarian neural regeneration, we monitored the regeneration of neuronal populations specifically labelled with antibodies against serotonin, allatostatin, neuropeptide F, GYRFamide and FMRFamide. We also characterized the regeneration of dopaminergic and octopaminergic cell populations by hybridization. Finally, we characterized the expression pattern in situ of a set of receptors for neurotransmitters, neuropeptides and hormones that are suggested to play a role in the regeneration process itself. Together , these data provide a more detailed description of the cellular events occurring during anterior and posterior CNS regeneration in planarians and provide the foundations for future mechanistic studies into the regeneration process in this important model system. [ABSTRACT FROM AUTHOR]