Lecture 3: Development of the Hypothalamus

Question 1

Describe the general position of the hypothalamus in the brain

Answer 1

The hypothalamus is located behind and upwards of the back of the soft pallet.
It occupies a very ventral position in the brain.

Question 2

Name some of the core homeostatic functions that the hypothalamus controls

Answer 2

Temperature, circadian cycle, electrolyte balance, reproduction, metabolism, stress, growth, desires and mood.

Question 3

When and in what form was progress first made into understanding the development of the hypothalamus?

Answer 3

In 1996 during loss of function studies of Shh. The strongest phenotype was the dysmorphology of the forebrain.
In 2000 it was found that approximately 1 in 16000 live births developed with genetic mutations in shh/shh signalling pathway components.
This focused attention on the PM as this part of the axial mesoderm expresses shh & underlies the anterior-most part of the neural tube.
Experiments in 2000-05 showed that PM shh induced fan-shaped cells in the neural plate above it.

Question 4

Why did the early experiments focus attention on the ventral midline of the brain?

Answer 4

This was thought of as a floor plate-like structure due to it expressing the same molecular markers for a brief time.

Question 5

What was shh doing in the anteriormost tip of the prechordal mesoderm?

Answer 5

Diffusing in arcs causing both a DV pattern of expression and arcs of gene expression which are progenitor territories.

Question 6

By what are these shh patterns become rapidly obscured &why?

Answer 6

By chaotic clustering of TFs around the edges of the floor plate territory due to up regulation of FGF10+ cells in the floor plate type structure.