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mab21-l3 regulates cell fate specification of multiciliate cells and ionocytes

Chika Takahashi1, Morioh Kusakabe2, Toshiyasu Suzuki1

  • 1Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.

Nature Communications
|January 20, 2015
PubMed

Insights

The mab21-l3 gene links the Notch pathway to multiciliated cell (MCC) and ionocyte development. This study reveals mab21-l3 is essential for these cell types and acts downstream of Notch signaling.

Area of Science:

  • Developmental biology
  • Cell biology
  • Molecular biology

Background:

  • Notch pathway signaling commonly suppresses multiciliated cell (MCC) and ionocyte differentiation in developing epithelia.
  • Distinct master regulators govern MCC and ionocyte specification, implying a common upstream regulator.
  • The molecular link between Notch signaling and these specific cell fate decisions remains largely unknown.

Purpose of the Study:

  • To identify and characterize a novel regulator connecting Notch pathway activity to MCC and ionocyte cell fate.
  • To elucidate the role of the mab21 family gene, mab21-l3, in epithelial cell differentiation.
  • To investigate the downstream effects of mab21-l3 in Xenopus and mouse models.

Main Methods:

  • Expression analysis of mab21-l3 in Xenopus embryonic epidermis and mouse tracheal epithelial cells.
  • Knockdown experiments of mab21-l3 in Xenopus to assess its role in MCC and ionocyte development.
  • Conditional gain-of-function studies of mab21-l3 in Xenopus to rescue Notch-induced cell fate suppression.
  • Analysis of master gene expression for MCC and ionocyte lineages.

Main Results:

  • mab21-l3 is specifically expressed in MCCs and ionocytes and is downregulated by the Notch pathway in both Xenopus and mouse models.
  • mab21-l3 knockdown in Xenopus leads to a significant loss of MCCs and ionocytes, with downregulation of their respective master genes.
  • Conditional mab21-l3 expression rescues the Notch-mediated suppression of MCC and ionocyte differentiation in Xenopus.
  • mab21-l3 is crucial for MCC differentiation in mouse tracheal epithelial cells.

Conclusions:

  • The mab21 family gene, mab21-l3, acts as a critical downstream mediator of Notch pathway signaling in the specification of MCCs and ionocytes.
  • mab21-l3 is essential for the development and differentiation of both MCCs and ionocytes across different species.
  • This study identifies mab21-l3 as the missing link connecting Notch signaling to these specific epithelial cell fates.

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