Review
The Ins and Outs of Notch Signaling

https://doi.org/10.1006/mcne.1997.0612Get rights and content

Abstract

The Notch gene encodes a cell surface protein that regulates cell fate choices in vertebrates and invertebrates. Given the wide variety of cell types influenced by Notch, it would seem that the signal relayed through Notch activation is not an instructive one per se. Rather, Notch signaling is thought to influence the cell's ability to respond to instructive signals responsible for specific cell fates. Expression and functional studies of Notch support this idea; however, the possibility of additional functions for Notch cannot be excluded. Much of what we know about the Notch signaling pathway comes from studies withDrosophilaNotch and theCaenorhabditis elegansNotch-related genes lin-12 and glp-1. With the isolation of multiple vertebrate Notch genes we are beginning to understand and define Notch signaling in vertebrates as well. A number of excellent reviews have been published summarizing the current status of Notch/LIN-12/GLP-1 signaling inDrosophilaandC. elegans,as well as recent findings with the vertebrate counterparts. Here I review the structure of the various Notch proteins and their putative ligands, and discuss possible interactions between Notch, its ligands, and other cellular components that affect Notch signal transduction. A role for Notch signaling during normal development and in disease processes is discussed in an accompanying review by T. Gridley (1997,Mol. Cell. Neurosci.9:103–108).

References (122)

  • M. Guo et al.

    tramtrack acts downstream of numb to specify distinct daughter cell fates during asymmetric cell divisions in the Drosophila PNS

    Neuron

    (1995)
  • M. Guo et al.

    Control of daughter cell fates during asymmetric division: Interaction of Numb and Notch

    Neuron

    (1996)
  • M. Haenlin et al.

    Genomic regions regulating early embryonic expression of the Drosophila neurogenic gene Delta

    Mech. Dev.

    (1994)
  • P. Heitzler et al.

    The choice of cell fate in Drosophila neuroepithelium

    Cell

    (1991)
  • Y.N. Jan et al.

    Maggot's hair and bug's eye: Role of cell interactions and intrinsic factors in cell fate specification

    Neuron

    (1995)
  • M.R. Kelley et al.

    Mutations altering the structure of epidermal growth factor-like coding sequences at the Drosophila Notch locus

    Cell

    (1987)
  • C. Kenyon

    A perfect vulva every time: Gradient and signaling cascades in C. elegans

    Cell

    (1995)
  • R. Kopan et al.

    The Notch pathway: Democracy and aristocracy in the selection of cell fate

    Curr. Opin. Neurobiol.

    (1996)
  • M. Lardelli et al.

    Expression of the Notch3 intracellular domain in mouse central nervous system progenitor cells is lethal and leads to disturbed neural tube development

    Mech. Dev.

    (1996)
  • J.E. Lee

    Basic helix–loop–helix genes in neural development

    Curr. Opin. Neurobiol.

    (1997)
  • J. Lewis

    Neurogenic genes and vertebrate neurogenesis

    Curr. Opin. Neurobiol.

    (1996)
  • C.E. Lindsell et al.

    Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand–receptor pairs that may function in neural development

    Mol. Cell. Neurosci.

    (1996)
  • C.E. Lindsell et al.

    Jagged: A mammalian ligand that activates Notch1

    Cell

    (1995)
  • Q. Ma et al.

    Identification of neurogenin, a vertebrate neuronal determination gene

    Cell

    (1996)
  • C.C. Mello et al.

    The maternal genes apx-1 and glp-1 and establishment of dorsal–ventral polarity in the early C. elegans embryo

    Cell

    (1994)
  • M.A. Muskavitch

    Delta-Notch signaling andDrosophila

    Dev. Biol.

    (1994)
  • A. Myat et al.

    A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogenesis

    Dev. Biol.

    (1996)
  • Z. Paroush et al.

    Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins

    Cell

    (1994)
  • J.W. Posakony

    Nature versus nurture: Asymmetric cell divisions in Drosophila bristle development

    Cell

    (1994)
  • I. Rebay et al.

    Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor

    Cell

    (1993)
  • I. Rebay et al.

    Specific EGF repeats of Notch mediate interactions with Delta and Serrate: Implications for Notch as a multifunctional receptor

    Cell

    (1991)
  • E. Robey et al.

    An activated form of Notch influences the choice between CD4 and CD8 T cell lineages

    Cell

    (1996)
  • S. Artavanis-Tsakonas et al.

    Notch signaling

    Science

    (1995)
  • J. Aster et al.

    Functional analysis of the TAN-1 gene, a human homolog of Drosophila notch

    Cold Spring Harbor Symp. Quant. Biol.

    (1994)
  • C.P. Austin et al.

    Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch

    Development

    (1995)
  • J.D. Axelrod et al.

    Interaction between Wingless and Notch signaling pathways mediated by dishevelled

    Science

    (1996)
  • A.M. Bailey et al.

    Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity

    Genes Dev.

    (1995)
  • A.G. Bang et al.

    The Drosophila gene Hairless encodes a novel basic protein that controls alternative cell fates in adult sensor organ development

    Genes Dev.

    (1992)
  • L.W. Berry et al.

    Germ-line tumor formation caused by activation of glp-1, a Caenorhabdtis elegans member of the Notch family of receptors

    Development

    (1997)
  • B. Bettenhausen et al.

    Transient and restricted expression during mouse embryogenesis of Dl11, a murine gene closely related to Drosophila Delta

    Development

    (1995)
  • C. Brou et al.

    Inhibition of the DNA-binding activity of Drosophila suppressor of hairless and of its human homolog, KBF2/RBP-J kappa, by direct protein–protein interaction with Drosophila hairless

    Genes Dev.

    (1994)
  • I. Busseau et al.

    A member of the Notch group of interacting loci, deltex encodes a cytoplasmic basic protein

    Genetics

    (1994)
  • A. Chitnis et al.

    Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta

    Nature

    (1995)
  • A. Chitnis et al.

    Sensitivity of proneural genes to lateral inhibition affects the pattern of primary neurons in Xenopus embryos

    Development

    (1996)
  • S. Christensen et al.

    lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H)

    Development

    (1996)
  • J.P. Couso et al.

    The wingless signalling pathway and the patterning of the wing margin in Drosophila

    Development

    (1994)
  • S.L. Crittenden et al.

    GLP-1 is localized to the mitotic region of the C. elegans germ line

    Development

    (1994)
  • J.L. de la Pompa et al.

    Conservation of the Notch signalling pathway in mammalian neurogenesis

    Development

    (1997)
  • R.J. Diederich et al.

    Cytosolic interaction between deltex and Notch ankyrin repeats implicates deltex in the Notch signaling pathway

    Development

    (1994)
  • D. Doherty et al.

    Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand, in Drosophila wing formation

    Genes Dev.

    (1996)
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