Notch (named after notch in wing)

S, Artavanis-Tsakonas et al., Notch signalling, Science 268 225-232, 1995
Here's the scheme:
Multicellular development: sequential action of genes
maternal-effect: (1) anterior, (2) posterior, (3) terminal, (4) dorso-ventral
zygotic: (1) gap, (2) pair rule, (3)segment polarity
then homeotic assigns segments
Specification
(1) lineage
(2) regulation by cell interaction
(i) "lateral" specification if cells were initially equivalent
(ii) ""Inductive" if nonequivalent
Notch in Drosophila and homologues in vertebrates
also lin-12 and glp-1 in C. elegans
TRANSPARENCY 300 kD w/ 36 EGF (epidermal growth factor) repeats
3 cysteine rich Notch/Lin-12 repeats
6 Ankyrin repeats
1 PEST (signal sequence for ubiquitinization)
ectoderm -> neuroblasts (delaminate)
dermmblasts
pro-neural express achaete-scute transcription factors
without Notch, all ectodermal cells continue to express
So Notch was called "neurogenic" but that does injustice to its multitude effects
Participates in both lateral and inductive signalling
in C. elegans, participates in anchor cell, uterine precursor & vulval precursor
vertebrate throughout development and in certain neoplasms
ligands shown in figure
some question about scabrous product involved in R8 spacing
also possibility of wingless product related to Wnt-1 proto-oncoprotein
pathway (TRANSPARENCY)
deltex encodes 737 a.a. cytoplasmic protein binds to ankyrin repeats
Suppressor of Hairless - product like several transcription factors
does detex multimerize Notch to interfere with Su(H)?
Hairless (novel basic protein) vs its supressor - adult sensory
Enhancer of split "complex" - 7 bHLH and another protein
mastermind shows up in modifier screens

J. D. Axelrod et al. Interaction between Wingless and Notch signalling pathways mediated by disheveled, Science 371 1826-1832, 1996
S.S.Blair, Notch and Wingless signals collide Science 371 1822-1823, 1996
ed. by P. Szuromi Inhibited by cross talk (This week in Science) Science 371 1785, 1996
The last paper was cautious in implicating wingless, here it is shown
TRANSPARENCY
dishevelled (dsh) protein of unknown protein
zeste-white 3 (zw3) = shaggy serine-threonine kinases
armadillo (arm) homologue of b-catenin (intracellular attachment protein)
(hooks membrane things to actin)
wingless signal is not known
Dsh inhibits Notch
Sgg-Zw3 phosphorylates and inactivates Arm

H. Kramer, RIPping notch apart: a new role for endocytosis in signal transduction? Science's STKE
DSL = Delta Serrate (Drosophila) Lag-2 (C. elegans
RIP = regulated intramembrane proteolysis
CSL = CBF1, Su(H), Lag-1 [CSL is a family of DNA binding proteins]
S1 cleavage makes notch receptor, S2 cuts off all but 12 a.a's on outside, S3 releases intracellular transcriptionally active domain (ICD)
S3 cut made by enzyme like gamma-secretase (Presenilin) thaty cuts APP (amyloid precursor protein) to make beta-amyloid that contributes to extracellular plaques

References

S, Artavanis-Tsakonas et al., Notch signalling, Science 268 225-232, 1995

J. D. Axelrod et al. Interaction between Wingless and Notch signalling pathways mediated by disheveled, Science 371 1826-1832, 1996

S.S.Blair, Notch and Wingless signals collide Science 371 1822-1823, 1996

ed. by P. Szuromi Inhibited by cross talk (This week in Science) Science 371 1785, 1996

H. Kramer, RIPping notch apart: a new role for endocytosis in signal transduction? Science's STKE


This page was last updated on March 14, 2002

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