Notch and Ras promote sequential steps of excretory tube development in C. elegans

Ishmail Abdus-Saboor, Vincent P. Mancuso, John I. Murray, Katherine Palozola, Carolyn Norris, David H. Hall, Kelly Howell, Kai Huang, Meera V. Sundaram

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Receptor tyrosine kinases and Notch are crucial for tube formation and branching morphogenesis in many systems, but the specific cellular processes that require signaling are poorly understood. Here we describe sequential roles for Notch and Epidermal growth factor (EGF)-Ras-ERK signaling in the development of epithelial tube cells in the C. elegans excretory (renallike) organ. This simple organ consists of three tandemly connected unicellular tubes: the excretory canal cell, duct and G1 pore. lin-12 and glp-1/Notch are required to generate the canal cell, which is a source of LIN-3/EGF ligand and physically attaches to the duct during de novo epithelialization and tubulogenesis. Canal cell asymmetry and let-60/Ras signaling influence which of two equivalent precursors will attach to the canal cell. Ras then specifies duct identity, inducing auto-fusion and a permanent epithelial character; the remaining precursor becomes the G1 pore, which eventually loses epithelial character and withdraws from the organ to become a neuroblast. Ras continues to promote subsequent aspects of duct morphogenesis and differentiation, and acts primarily through Raf-ERK and the transcriptional effectors LIN-1/Ets and EOR-1. These results reveal multiple genetically separable roles for Ras signaling in tube development, as well as similarities to Ras-mediated control of branching morphogenesis in more complex organs, including the mammalian kidney. The relative simplicity of the excretory system makes it an attractive model for addressing basic questions about how cells gain or lose epithelial character and organize into tubular networks.

Original languageEnglish (US)
Pages (from-to)3545-3555
Number of pages11
Issue number16
StatePublished - Aug 15 2011


  • C. elegans
  • Ras
  • Tubulogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology


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