In the Hedgehog signalling pathway,
Patched (PTCH) normally inhibits Smoothened (SMO) by preventing its
accumulation in the primary cilium. When Hedgehog ligand binds PTCH, SMO
translocates to the cilium leading to the activation of Gli transcription
factors. In a mouse model, researchers introduce the SmoM2 mutation, which
constitutively activates SMO, independent of PTCH inhibition.

Which of the following outcomes is
most likely in these mice?

Question

In the Hedgehog signalling pathway,
Patched (PTCH) normally inhibits Smoothened (SMO) by preventing its
accumulation in the primary cilium. When Hedgehog ligand binds PTCH, SMO
translocates to the cilium leading to the activation of Gli transcription
factors. In a mouse model, researchers introduce the SmoM2 mutation, which
constitutively activates SMO, independent of PTCH inhibition.

Which of the following outcomes is
most likely in these mice?

Accepted Answer

Constitutive
SMO activation leads to continuous Gli target gene expression, promoting basal
cell carcinoma and medulloblastoma

Answer

Hedgehog signalling
becomes independent of ciliary localization, but Gli remains partially
repressed due to inhibitory Gli2 processing

Answer

SMO activation
triggers negative feedback that enhances GLI3 repressor formation, preventing
tumor formation

Answer

Hedgehog target genes
are suppressed because PTCH continuously inhibits SMO, preventing
transcriptional activation

Crowdly

In the Hedgehog signalling pathway, Patched (PTCH) normally inhibits Smoothened...

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