Olfactory Sensory Neurons Control Dendritic Complexity of Mitral Cells via Notch Signaling

PLoS Genet. 2016 Dec 27;12(12):e1006514. doi: 10.1371/journal.pgen.1006514. eCollection 2016 Dec.

Abstract

Mitral cells (MCs) of the mammalian olfactory bulb have a single primary dendrite extending into a single glomerulus, where they receive odor information from olfactory sensory neurons (OSNs). Molecular mechanisms for controlling dendritic arbors of MCs, which dynamically change during development, are largely unknown. Here we found that MCs displayed more complex dendritic morphologies in mouse mutants of Maml1, a crucial gene in Notch signaling. Similar phenotypes were observed by conditionally misexpressing a dominant negative form of MAML1 (dnMAML1) in MCs after their migration. Conversely, conditional misexpression of a constitutively active form of Notch reduced their dendritic complexity. Furthermore, the intracellular domain of Notch1 (NICD1) was localized to nuclei of MCs. These findings suggest that Notch signaling at embryonic stages is involved in the dendritic complexity of MCs. After the embryonic misexpression of dnMAML1, many MCs aberrantly extended dendrites to more than one glomerulus at postnatal stages, suggesting that Notch signaling is essential for proper formation of olfactory circuits. Moreover, dendrites in cultured MCs were shortened by Jag1-expressing cells. Finally, blocking the activity of Notch ligands in OSNs led to an increase in dendritic complexity as well as a decrease in NICD1 signals in MCs. These results demonstrate that the dendritic complexity of MCs is controlled by their presynaptic partners, OSNs.

MeSH terms

  • Animals
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism
  • Gene Expression Regulation, Developmental
  • Jagged-1 Protein / biosynthesis
  • Jagged-1 Protein / genetics
  • Mice
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Olfactory Bulb / growth & development
  • Olfactory Bulb / metabolism*
  • Olfactory Receptor Neurons / cytology
  • Olfactory Receptor Neurons / metabolism*
  • Receptor, Notch1 / biosynthesis
  • Receptor, Notch1 / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*

Substances

  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Maml1 protein, mouse
  • Notch1 protein, mouse
  • Nuclear Proteins
  • Receptor, Notch1
  • Transcription Factors

Grant support

This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Neural Diversity and Neocortical Organization” JP25123701 from MEXT, Japan, and JSPS KAKENHI Grant (https://www.jsps.go.jp/english/e-grants/) Numbers JP24300116, JP26640026 and JP16K15166 to TS, and JP26460269 to AB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.