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Genetic regulation of planarian head morphogenesis during regeneration

Planarians possess amazing powers of regeneration and can rebuild any lost body part. The regenerative process, based on stem cells (neoblasts), is mediated by the formation of a blastema. During head regeneration, a complete functional brain, as well as the cephalic sensory structures, including eyes, are rebuilt. Recently, the characterization of a number of neural genes has revealed the complexity of the planarian central nervous system (CNS) at both the molecular and structural levels. In this review, special attention is addressed to planarian eye regeneration, and we cloned and characterized several of the genes involved in this process. Our work demonstrated that regulatory genes similar to those found in a variety of organisms, such as Pax6, eya, and six, orchestrate eye regeneration in planarians. However, the strategies that control this process may not be conserved completely, as demonstrated by our RNA interference (RNAi)‐based functional studies. We also performed a comprehensive search of eye‐related genes generating reciprocal suppressive subtractive hybridization (SSH) cDNA libraries, taking advantage from the use of the RNAi‐induced functional ablation of six‐1, a gene expressed only in the photoreceptors, to obtain planarians devoid of eyes. We cloned several genes with a role in a variety of cellular functions, as well as gene products of unknown function. The information gathered from this study provides new resources to better understand the molecular mechanisms of regeneration in planarians.