ch23 neuron migration stem cells

8/9/2019 Ch23 Neuron Migration Stem Cells

1/22

Development

Neuron migration

Neurotrophins


2/22

Neurobiology BIO 475

Birth order and cell fate: cortex

!ase study: mammalian cerebral cortex

" cortex is layered structure

" distinct neuron types in each layer

" layers are formed se#uentially

Inside early$ outside late

li%e rings in a tree trun%

" different types of neurons are added in aprecise se#uence


3/22


&ayers in cerebral cortex

'everal layers I: incoming axons

II$ III: pyramidal cell

layers

" pro(ect to neighboringcortex

I): stellate cells

" local pro(ections

)$)I: pyramidal cells " *ro(ect out of cortex

+ig ,-.


4/22

!ortical layers develop Neurons populate in an inside/out se#uence-

&ater born neurons must migrate past earlierborn-

&ayer identity is a function of both neuron andenvironment-


5/22


!ortical layers: inside/out order Determining birth dates of neurons: pulse/label strategy

" in(ect radioactive thymidine in short pulse

" only cells in '/phase 0ill incorporate into DN1

" cells that soon terminally divide are heavily labeled

" cells that continue to cycle 0ill dilute label

" pulse label at various times during development$ collect and section brain after birth

" In 0hich layer do labeled cells end up2

3esult in mon%ey: " early born deep

" late born superficial

'anes$ Development ofthe Nervous 'ystem


6/22


Neurons reach their layer by climbing radial glia

ethod for both cortex andcerebellum-

Neurons and glia interact toguide neuron migration

3eeler mouse has migrationdefect-


7/22


6uman cortical migration

defects Defects in cortical migration are fairly common

" heterotopias:

!lumps of neurons caused by regional defects in corticallayering

" 859 of childhood epilepsy patients have heterotopias &arge enough to be visible in 3I brain scans

!lumps of neurons form abnormal connections$ 0hich maycause epileptic firing patterns

&issencephalydouble cortex syndromes

" massive defects in cortical neuron migration " ;smooth brain< phenotype$ 0ith thic%er cortex$ or less severe

resulting from extra layers of cells ;hung up<


8/22


=ato and Dobyns$ 6uman olecular >enetics$ 8??@$ )ol- A8$ 3evie0 Issue A R89-R96

Lissencephaly and the molecular basis of neuronal migration


9/22


6uman cortical migration defects

&issencephalydouble cortexsyndromes " massive defects in cortical

neuron migration

" ;Double cortex<

Outside layer present But inner dar% area is

abnormal

" ;smooth brain< phenotype$ 0iththic%er cortex$ or less severeresulting from extra layers of cells

;hung up<


10/22


1dult neural stem cells Ongoing neurogenesis in the brain 0o main locations in brain

" )entricular Cone of cortex igrate to olfactory bulbs " 6ippocampus

*ossible role in memory formation " !oncept: stem cell niche

a special place that promotes stem cells 'timulates stem cell properties$ controls ho0 many divide and ho0

many differentiate


11/22

Neural stem cells 'tem cell definition

" 1dult neurogenesis: discovery " *roliferation slo0E$ potential$ niche " &ocations in human brain

'ignals that regulate neurogenesis " Fxercise$ depresssionstress$ anti/depressants

+unction of ne0 neurons " Need to migrate homingE$ differentiate$ integrate into existing circuits " *hysiologically different: more easily excited$ more inputs " 3e#uired for ne0 memory formation

i*'!s " 3ecipes for inducing stem cells

" 3ecipes for differentiating stem cells " *atient/derived i*'!s: differentiated neurons as disease models

Neural stem cells " *romise: *ar%insons$ 1&' " *roblemslimitations


12/22

8?A8 Nobel *riCe: Induced

pluripotent stem cells

Gohn >urdon$ !ambridge " In A,.?s: nuclear

transplantation " +rog egg: removed nucleus " 3eplaced 0ith a ne0 cell

nucleus " Ne0 nucleus 0as able to drive

development to complete frog

Nucleus retains full potency

'hinya Hamana%a$ =yoto niv " Discovered set of transcription

factors expressed by stem cells " ransfected them into fibroblastss%in cellsE

" urned them into stem cells

ature cells reprogrammed tobe pluripotent: " able to differentiate into any cell

type


13/22

>rades may not be good

predictors of success

John Gurdon’s biology report

card, Eton College, 1949


14/22

Neurobiology BIOL 475

6ippocampus: center for adult

neurogenesis

ain region of adult neurogenesis

!ontains neural progenitors

In rodents$ about ,$??? ne0 neurons bornper day

!ould this be associated 0ith memory

function of hippocampus2


15/22

Neurobiology BIOL 475

Ne0 neurons re#uired for

memory *revent neurogenesis$ prevent ne0 spatial

memory

Fxperiment in young adult mice

!lue that adult neurogenesis may have

functional role in long term memory

1- Irradiate to %illadult neural

progenitors stem

cellsE

B- A 0ee%:able to learn

maCe

!- est at 8$@$4 0ee%s- +ailedto remember location of

platformJ disrupted long term

memory


16/22

Khat is neuroscience2

'tudy of the nervoussystem

" *hysics$ chemistry

" >enetics$ molecularbiology " cell biology$ developmental

biology " physiology$ anatomy$

endocrinology " psychology$ behavior$

neurology " 1nimal behavior$ evolution

'lide A. BIO& 475.75 Neurobiology

Diffusion tensor 3I of human brain


17/22

- eurons:functional units

of the nervoussystem

Ke 0ill learn:

ni#ue cell biologyof neurons

6o0 neurons

transmit electrical

signals

6o0 neurons signal

to each other

'lide A7 BIO& 475.75 Neurobiology


18/22

'ystems: net0or%s of neurons

control sensory perception Input: sensory

systems

" 'ense external

stimulus transduction *hoton$ chemical$

sound 0ave$ touch

" !hange into signals

0ithin net0or%s

" !reate an internal

representation of

outside 0orld

'lide AL BIO& 475.75 Neurobiology


19/22

M and control movement otor system:

" !ontrols muscle contractions " 3eflexes$ coordinated movements

'lide A, BIO& 475.75 Neurobiology


20/22

ental illness and neurological

diseases Devastating diseases

" Often life/long

" Impacts across society

'ome gain uni#ue abilities

!an 0e understand their

causes2

" >enes$ molecules$ neurons

!an biology help to

discover treatments2

'lide 8? BIO& 475.75 Neurobiology


21/22

6o0 does the brain build itself2 Development of the brain in the

embryo

" Khat defines the nervous system2

" 6o0 are neurons born2

" 6o0 do neurons connect2 he dynamic brain: learning and

memory

" he brain changes its o0n

structure " Ne0 neurons are born

" !onnections are made and lost

'lide 8A BIO& 475.75 Neurobiology


22/22

Our Neurobiology semester

Neurons

1ction potentials

'ynapses

Fxam A 'ept 85

'ection A

'lide 88 BIO& 475.75 Neurobiology

'ection 8 'ection @

'ensory systems

!hemical$ visual$auditory$ somatic

otor systems

Fxam 8 Oct @?

ental illness

&earning andmemory

Neural development

+inal Dec AL

ch23 neuron migration stem cells

Documents