L5

Question 1

why is it important to understand the behaviour, nature and control of tissues and resident adult stem cells?

Answer 1

It is important to understand these behaviours as many cells can be regenerated from stem cell populations
- understanding the nature of stem cells can lead to potential therapies

Question 2

what are the cells before B cells develop?

Answer 2

endodermal progenitor
pancreatic progenitor
B cell

Question 3

where are the leptin responsive neurons situated and what are they?

Answer 3

• in the arcuate nucleus of the hypothalamus

- NPY and pomc neurons

Question 4

how does leptin affect NPY neurons?

Answer 4

• leptin inhibits NPY neurons

- NPY is a neuropeptide which coordinates the brain activities which stimulate food intake and reduce energy expenditure

Question 5

How does leptin affect pomc neurons?

Answer 5

• leptin stimulates/activates pomc neurons
• pomc is a neurohormone which coordinates the brain to stimulate activities which reduce food intake and increase energy expenditure.

Question 6

where are pomc and NPY neurons generated from?

Answer 6

Generated from radial glial like cells (tanycytes) which are hypothalamic stem cells
- cell body at 3rd ventricle and projection is used as a scaffold for differentiating daughter cells to migrate laterally into the arcuate nucleus where they can differentiate into a pomc or NPY neuron

Question 7

what is the emerging idea about pomc/nyp neuron generation throughout life?

Answer 7

• throughout life glucose requirements change (e.g. with hormones, puberty, pregnancy)
• pomc and NPY neurons could be generated from hypothalamic stem cells during adult life to anticipate/respond to changing needs of the body

Question 8

what are stages and markers from a hypothalamic stem cell to a pomc/npy neuron?

Answer 8

hypothalamic stem cell - fgf10, pea3, glast1
arcuate progenitor cell - islet-1
pomc/npy neuron

Question 9

what are functions of fgf and shh in formation of a pomc/npy neuron?

Answer 9

fgf causes division of hypothalamic stem cells

Shh causes differentiation into arcuate progenitor cell

Question 10

what happens if the arcuate nucleus is ablated?

Answer 10

there is a decrease in pomc/npy neurons and arc progenitor cells

• over time stem cells will replace arc progenitors, pomc neurons and npy neurons

(show has regenerative capacity)

Question 11

what is islet -1 required for?

Answer 11

islet 1 is required for the identity of melanocortin (pomc) neurons and is critical for normal food intake and normal adiposity in adulthood

-Isl1 is necessary for hypthalamic pomc expression during embryogenesis

Question 12

what happens when isl1 is inactivated?

Answer 12

impairs pomc expression which results in hyperphagia and obesity

Question 13

when is isl1 detected in the hypothalamus?

Answer 13

detected before the onset of pomc expression

-pomc and islet1 are then coexpressed

Question 14

what transgenic line can lineage trace alpha tanycytes (hypothalamic stem cells)

Answer 14

Glast1:Cre-ERT2
- cre activated upon injection of tamoxifen
- crossed with transgenic line with
constitutive promoter: (lox) STOP (lox) :reporter gene
e.g. (rosa26:STOP:GFP)

Question 15

what happens to hypothalamic stem cells upon FGF1 infusion?

Answer 15

• is increased activity of tanycytes
• sustained remission of hyperglycemia in rodents
• immunohistochemistry detects c-fos in tanycytes
• diabetes remission
• cerebroventricular injection required (brain involved)

Question 16

what does c-fos mark?

Answer 16

c-fos marks cellular activation