13 Flashcards
Delta and Jagged ligands in us and Delta and ………………… in flies!
serrate
GAP junctions use —– signalling
Juxtacrine
What is found in glial cells and neruons?
high NOTCH concentrations in Glial
High Delta in Neurons
c. elegans are ? (sex related)
hermaphrodites
- start out as males and become females
Anchor cells secrete ?
LIN-3 (EGF)
If no LIN-3 cells will default to ?
Skin Cells (not vulval)
what is LET3? and what does it do?
LET-23 (RTK) on P6p picks up most of LIN-3 ligand –activates Delta ligands
LET23 is homologous to EGFR
what does delta signalling activate?
Delta signaling activates lin-12 (Notch) in neighboring P5p and P7p cells
EGF binds RTK (Let-23) & turns on —-?
Ras
–> MAPK pathway
EGF secreted from –?
AC (morphogen)
Signaling in Primary cell activates ?
Delta : –>
- Inhibits Notch
- lots of MAPK specifies primary fate
(in P6p cell)
—– specifies secindary cell fate?
Notch-Delta:
- reduces MAPK activity
Lateral Inhibition
Steps in the Sending Cell (Delta-Expressing Cell, Pro-Neural Fate)
The cell begins expressing Atoh1 (a pro-neural bHLH transcription factor).
Atoh1 upregulates Delta ligand
Delta binds to Notch receptors on neighboring cells.
This activates the Notch pathway in the receiving cell, leading to inhibition of its pro-neural fate.
The sending cell maintains high Atoh1 expression, committing to a neuronal (or sensory) fate.
Lateral Inhibition
Steps in the Receiving Cell (Notch-Activated Cell, Inhibited Fate):
Notch receptor binds to Delta from the sending cell.
Notch undergoes proteolytic cleavage by gamma-secretase, releasing the Notch Intracellular Domain (NICD).
NICD enters the nucleus and binds to transcription factors
This activates the transcription of Hes genes which act as transcriptional repressors.
Hes proteins inhibit Atoh1 expression
The receiving cell remains in an undifferentiated
What does Hes do?
Hes inhibits pro-neural factors like Atoh1
preventing neuronal differentiation in Notch-activated cells.
Notch is a —— (what type of protein(s))?
Notch is a tumor suppressor and a proto-oncogene!
Notch ligands = ?
Delta/Jagged (Serrate)
a secretase is part of the —– Family
ADAMs family
ADAM10 is a ?
A
Disintegrin
And a
Metalloprotease
What induces NICD?
y secretase complex cleaves Notch again to induce NICD
What does NICD stand for?
Notch Intracellular Domain
Notch-Delta Signaling Pathway
Delta binds to Notch, triggering activation.
a-secretase cleaves Notch’s extracellular domain, freeing it from Delta.
The Notch extracellular domain is endocytosed by the Delta-expressing cell.
The remaining Notch transmembrane fragment is cleaved by y-seccretase
This releases the Notch Intracellular Domain (NICD)
NICD enters the nucleus, binds transcription factors, and activates Hes gene transcription to inhibit pro-neural differentiation.
Presenilin & γ-Secretase Complex Localized to —–?
the Basal Body (near the Transition zone)
what is ARF4 and what does it do?
ARF4 (ADP-Ribosylation Factor 4) is a small GTPase in the Ras superfamily.
ARF4 ensures proteins like Smoothened (Smo) and other signalling molecules reach the primary cilium.
what keeps Delta Off?
Hes