title: Genome-wide analysis of the bHLH gene family in planarians identifies factors required for adult neurogenesis and neuronal regeneration.
abstract: In contrast to most well-studied model organisms, planarians have a remarkable ability to completely regenerate a functional nervous system from a pluripotent stem cell population. Thus, planarians provide a powerful model to identify genes required for adult neurogenesis in vivo. We analyzed the basic helix-loop-helix (bHLH) family of transcription factors, many of which are crucial for nervous system development and have been implicated in human diseases. However, their potential roles in adult neurogenesis or central nervous system (CNS) function are not well understood. We identified 44 planarian bHLH homologs, determined their patterns of expression in the animal and assessed their functions using RNAi. We found nine bHLHs expressed in stem cells and neurons that are required for CNS regeneration. Our analyses revealed that homologs of coe, hes (hesl-3) and sim label progenitors in intact planarians, and following amputation we observed an enrichment of coe(+) and sim(+) progenitors near the wound site. RNAi knockdown of coe, hesl-3 or sim led to defects in CNS regeneration, including failure of the cephalic ganglia to properly pattern and a loss of expression of distinct neuronal subtype markers. Together, these data indicate that coe, hesl-3 and sim label neural progenitor cells, which serve to generate new neurons in uninjured or regenerating animals. Our study demonstrates that this model will be useful to investigate how stem cells interpret and respond to genetic and environmental cues in the CNS and to examine the role of bHLH transcription factors in adult tissue regeneration.
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182, USA.
authors.forename: Martis W
authors.initials: MW
authors.lastname: Cowles
authors.forename: David D R
authors.initials: DD
authors.lastname: Brown
authors.forename: Sean V
authors.initials: SV
authors.lastname: Nisperos
authors.forename: Brianna N
authors.initials: BN
authors.lastname: Stanley
authors.forename: Bret J
authors.initials: BJ
authors.lastname: Pearson
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Zayas
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055106:Genome-Wide Association Study; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010932:Planarians / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins
keywords: Basic helix-loop-helix; Coe; Hes; Lophotrochozoan; Neoblasts; Neurogenesis; Planarians; Regeneration; Schmidtea mediterranea; Single-minded; Stem cells