Question

The Shh signalling pathway is important for patterning of multiple organs
during development, including the neural tube. Explain the molecular
basis of the Shh signalling pathway, and how it acts to regulate
patterning of the spinal cord. Include in your answer a brief description
of the spinal cord patterning you would expect if the Smoothened
protein were (a) completely inactive, and (b) permanently active.(500words)

Answer 1

Sonic Hedgehog signalling (Shh) pathway has a significat role when it comes to transduction of signals that regulate development of various tissues and organs in multicellular organisms. Shh protein is a key protein molecule that plays a role in signal transduction in the pathway. The pathway regulates processes post embryonic tissue regeneration and repair of tissues.It has a key role in neural tube development too.It affects polarity of the Central Nervous System and neural patterning. Upon activation,Shh protein's secretion in the neural tube, induction of different cells is induced including, motor neurons, floor plate cells, inter neurons.

Membrane anchored Shh protein is modified by lipid and triggers the signal transduction. Shh precursor is autoleaved into N and C terminal,C terminal Shh triggers autoproteolysis, resulting in cholesterol moeity addition to N terminal Shh.Post this, there is palmitoylation of Shh N terminal part which enhances its inductive activity.

Post Shh activation, smoothened protein (Smo) is activated. Activated Smo further transmits signals downstream, its activates several protein kinases which activate Ci proteins (cubitus interruptus) proteins, Gli (glioblastoma proteins).The Ci proteins then trigger transcriptiona; activation of genes that were suppressed by cleaved form of Ci.

When Smo is inactive, it cant bind to Costal-2 factor, and cant prevent Ci cleavage.