title: MAPK signaling is necessary for neurogenesis in Nematostella vectensis.
abstract: The nerve net of Nematostella is generated using a conserved cascade of neurogenic transcription factors. For example, NvashA, a homolog of the achaete-scute family of basic helix-loop-helix transcription factors, is necessary and sufficient to specify a subset of embryonic neurons. However, positive regulators required for the expression of neurogenic transcription factors remain poorly understood.
  
  
  
  We show that treatment with the MEK/MAPK inhibitor U0126 severely reduces the expression of known neurogenic genes, Nvath-like, NvsoxB(2), and NvashA, and known markers of differentiated neurons, suggesting that MAPK signaling is necessary for neural development. Interestingly, ectopic NvashA fails to rescue the expression of neural markers in U0126-treated animals. Double fluorescence in situ hybridization and transgenic analysis confirmed that NvashA targets represent both unique and overlapping populations of neurons. Finally, we used a genome-wide microarray to identify additional patterning genes downstream of MAPK that might contribute to neurogenesis. We identified 18 likely neural transcription factors, and surprisingly identified ~40 signaling genes and transcription factors that are expressed in either the aboral domain or animal pole that gives rise to the endomesoderm at late blastula stages.
  
  
  
  Together, our data suggest that MAPK is a key early regulator of neurogenesis, and that it is likely required at multiple steps. Initially, MAPK promotes neurogenesis by positively regulating expression of NvsoxB(2), Nvath-like, and NvashA. However, we also found that MAPK is necessary for the activity of the neurogenic transcription factor NvashA. Our forward molecular approach provided insight about the mechanisms of embryonic neurogenesis. For instance, NvashA suppression of Nvath-like suggests that inhibition of progenitor identity is an active process in newly born neurons, and we show that downstream targets of NvashA reflect multiple neural subtypes rather than a uniform neural fate. Lastly, analysis of the MAPK targets in the early embryo suggests that MAPK signaling is critical not only to neurogenesis, but also endomesoderm formation and aboral patterning.
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, PA, USA. layden@lehigh.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Layden
authors.affiliation: Université Nice Sophia Antipolis UMR 7284, CNRS UMR 7284, INSERM U1081, Institute for Research on Cancer and Aging, Nice, France.
authors.forename: Hereroa
authors.initials: H
authors.lastname: Johnston
authors.affiliation: Université Nice Sophia Antipolis UMR 7284, CNRS UMR 7284, INSERM U1081, Institute for Research on Cancer and Aging, Nice, France.
authors.forename: Aldine R
authors.initials: AR
authors.lastname: Amiel
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, PA, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Havrilak
authors.affiliation: The Whitney Marine Laboratory for Marine Science, University of Florida, St. Augustine, Florida, USA.
authors.forename: Bailey
authors.initials: B
authors.lastname: Steinworth
authors.affiliation: The Whitney Marine Laboratory for Marine Science, University of Florida, St. Augustine, Florida, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Chock
authors.affiliation: Université Nice Sophia Antipolis UMR 7284, CNRS UMR 7284, INSERM U1081, Institute for Research on Cancer and Aging, Nice, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Röttinger
authors.affiliation: The Whitney Marine Laboratory for Marine Science, University of Florida, St. Augustine, Florida, USA. mqmartin@whitney.ufl.edu.
authors.forename: Mark Q
authors.initials: MQ
authors.lastname: Martindale
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D003063:Cnidaria / Q000187:drug effects / Q000196:embryology / Q000201:enzymology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004475:Ectoderm / Q000187:drug effects / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054262:Gastrulation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008954:Models, Biological; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases