title: A Pitx transcription factor controls the establishment and maintenance of the serotonergic lineage in planarians.
abstract: In contrast to adult vertebrates, which have limited capacities for neurogenesis, adult planarians undergo constitutive cellular turnover during homeostasis and are even able to regenerate a whole brain after decapitation. This enormous plasticity derives from pluripotent stem cells residing in the planarian body in large numbers. It is still obscure how these stem cells are programmed for differentiation into specific cell lineages and how lineage identity is maintained. Here we identify a Pitx transcription factor of crucial importance for planarian regeneration. In addition to patterning defects that are co-dependent on the LIM homeobox transcription factor gene islet1, which is expressed with pitx at anterior and posterior regeneration poles, RNAi against pitx results in islet1-independent specific loss of serotonergic (SN) neurons during regeneration. Besides its expression in terminally differentiated SN neurons we found pitx in stem cell progeny committed to the SN fate. Also, intact pitx RNAi animals gradually lose SN markers, a phenotype that depends neither on increased apoptosis nor on stem cell-based turnover or transdifferentiation into other neurons. We propose that pitx is a terminal selector gene for SN neurons in planarians that controls not only their maturation but also their identity by regulating the expression of the Serotonin production and transport machinery. Finally, we made use of this function of pitx and compared the transcriptomes of regenerating planarians with and without functional SN neurons, identifying at least three new neuronal targets of Pitx.
authors.affiliation: Max Planck Research Group Stem Cells and Regeneration, Max Planck Institute for Molecular Biomedicine, Von-Esmarch-Strasse 54, 48149 Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: März
authors.forename: Florian
authors.initials: F
authors.lastname: Seebeck
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bartscherer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D054338:Cell Transdifferentiation / Q000235:genetics; D005786:Gene Expression Regulation; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D010932:Planarians / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012038:Regeneration / Q000235:genetics; D059326:Serotonergic Neurons / Q000166:cytology* / Q000378:metabolism*; D012701:Serotonin / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: D015415:Biomarkers; D060850:LIM-Homeodomain Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D012701:Serotonin
keywords: Islet1; Pitx; Planaria; Regeneration; Schmidtea mediterranea; Serotonergic neuron; Stem cell differentiation