title: Neuronal sources ofhedgehogmodulate neurogenesis in the adult planarian brain.
abstract: The asexual freshwater planarian is a constitutive adult, whose central nervous system (CNS) is in a state of constant homeostatic neurogenesis. However, very little is known about the extrinsic signals that act on planarian stem cells to modulate rates of neurogenesis. We have identified two planarian homeobox transcription factors,Smed-nkx2.1andSmed-arx, which are required for the maintenance of cholinergic, GABAergic, and octopaminergic neurons in the planarian CNS. These very same neurons also produce the planarianhedgehogligand (Smed-hh), which appears to communicate with brain-adjacent stem cells to promote normal levels of neurogenesis. Planarian stem cells nearby the brain express corehhsignal transduction genes, and consistenthhsignaling levels are required to maintain normal production of neural progenitor cells and new mature cholinergic neurons, revealing an important mitogenic role for the planarianhhsignaling molecule in the adult CNS.
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Ko W
authors.initials: KW
authors.lastname: Currie
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Molinaro
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Bret J
authors.identifier: http://orcid.org/0000-0002-3473-901X
authors.initials: BJ
authors.lastname: Pearson
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D010986:Platyhelminths / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors
keywords: developmental biology; flatworms; planarians; schmidtea mediterranea; stem cells; triclads