title: Insm1 promotes the transition of olfactory progenitors from apical and proliferative to basal, terminally dividing and neuronogenic.
abstract: BACKGROUND
  Insm1 is a zinc-finger transcription factor transiently expressed throughout the developing nervous system in late progenitors and nascent neurons. Insm1 is also highly expressed in medulloblastomas and other neuroendocrine tumors.
  
  
  RESULTS
  We generated mice lacking the Insm1 gene and used them to elucidate its role in neurogenic proliferation of the embryonic olfactory epithelium. We found that deletion of Insm1 results in more apical cells and fewer nascent and mature neurons. In the embryonic olfactory epithelium of Insm1 mutants we detect fewer basal progenitors, which produce neurons, and more apical progenitors, which at this stage produce additional progenitors. Furthermore, in the mutants we detect fewer progenitors expressing NEUROD1, a marker of terminally dividing, neuronogenic (neuron-producing) progenitors (immediate neuronal precursors), and more progenitors expressing ASCL1, a marker of the transit amplifying progenitors that migrate from the apical to the basal edges of the epithelium while dividing to generate the terminal, neuronogenic progenitors. Finally, with timed administration of nucleoside analogs we demonstrate that the Insm1 mutants contain fewer terminally dividing progenitors at embryonic day 12.5.
  
  
  CONCLUSIONS
  Altogether, these results suggest a role for Insm1 in promoting the transition of progenitors from apical and proliferative to basal, terminal and neuronogenic. This role appears partially conserved with that of its nematode ortholog, egl-46. The similar effects of Insm1 deletion on progenitors of embryonic olfactory epithelium and cortex point to striking parallels in the development of these neuroepithelia, and particularly between the basal progenitors of olfactory epithelium and the subventricular zone progenitors of cortex.
authors.affiliation: Department of Anesthesiology, Northwestern University Feinberg School of Medicine, 303 E, Chicago Avenue, Ward 10-070, Chicago, IL 60611, USA.
authors.forename: Jason N
authors.initials: JN
authors.lastname: Rosenbaum
authors.forename: Anne
authors.initials: A
authors.lastname: Duggan
authors.forename: Jaime
authors.initials: J
authors.lastname: García-Añoveros
mesh_terms: D000367:Age Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D019394:Ki-67 Antigen / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009154:Mutation / Q000235:genetics; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics*; D009833:Olfactory Pathways / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004268:DNA-Binding Proteins; D015259:Dopamine Agents; D019394:Ki-67 Antigen; D007980:Levodopa; D012097:Repressor Proteins; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C477059:Insm1 protein, mouse