development of the nervous system – 2

12th August 2013 Bio 334 - Neurobiology I - Development of nervous systems 2 1

Development of the nervous system – 2

Raghav RajanBio 334 – Neurobiology I

August 12th 2013


Neural tube, neural crest, etc. form

● Neural tube gives rise to CNS – brain and spinal cord

● Neural crest cells give rise to PNS

http://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Peripheral_nervous_system

http://en.wikipedia.org/wiki/Central_nervous_system


Neural tube divides early on into 3 distinct parts – forebrain, midbrain, hindbrain

● Tripartite organisation of brain – highly conserved


3 becomes 5 and then .....

http://www.highlands.edu/academics/divisions/scipe/biology/faculty/harnden/2121/images/brainves.jpg


Morphogen gradients – something that has been used many many times in development

● Diffusible secreted molecule

● Can activate different sets of transcriptional targets and therefore specify identity based on position

The intrepretation of morphogen gradients. Ashe and Briscoe. Development 2006http://dev.biologists.org/content/133/3/385.full.pdf+html


Interpreting morphogen gradients

● Many different ways to sense morphogen gradients

● Organizer – a piece of tissue that can

The intrepretation of morphogen gradients. Ashe and Briscoe. Development 2006http://dev.biologists.org/content/133/3/385.full.pdf+html


Insect segmental identity provides clues to setting up regional specialization and identity

● Progressively subdividing the embryo into smaller and smaller segments

● Homeotic (HOX) gene expression controlled by pair-rule genes and segment polarity genes


Eliminating hox gene cluster makes all segments look alike

● Tribolium● Number of segements normal● All of them have antennal segment morphology


Spatial order of HOX genes on the chromosome is correlated with expression along A-P axis

● HOX genes highly conserved

● Code for Homeodomain class of transcription factors

● Mouse – paralogous groups – eg: hoxa4, hoxb4, hoxc4, hoxd4

● Animals without such well-organized Hox clusters have perfectly good A-P axis


Vertebrate Hox gene function has been studied extensively in the hindbrain


Cranial nerves originate in the hindbrain and innervate muscles of the head

● Rhombomeres – segments of the hindbrain

● Cranial nerves – axons of motor nerves and sensory axons from neurons in the dorsal root ganglia

● Trigeminal – control jaw muscles

● Adbucens – control eye muscles


Elimination of hoxa1 in mice results in loss of r5

● Existence of paralogous groups provides some redundancy● Facial nerve defective, no abducens nerve


Without Hox genes, “default” state of hind brain is rhombomere 1

● Pbx, meis – homeodomain proteins – that significantly enhances specificity of hox genes for their promoter


Vertebrates may use different mechanisms to define the pattern of Hox gene expression

● Retinoic acid – a derivative of Vitamin A

● Powerful teratogen, causes birth defects

● Normally, gradient of RA with RA levels very high in posterior portion of Xenopus embryos

● Treatment with RA results in inhibition of anterior Hox gene expression and loss of anterior parts of nervous system

● RA gradient generated by mesoderm adjacent to neural tube


Nieuwkoop – activator-transformer hypotheis for specification of anterior-posterior axis

● Transplanted small pieces of ectodermal tissue from one embryo into a host at various positions in the A-P axis

● In anterior – made forebrain

● In posterior – made forebrain as well as hindbrain and spinal cord

● Activators: noggin, chordin, etc.

● Transformers: Retinoic acid, Wnt, FGFs

https://www.ucl.ac.uk/cdb/research/stern/stern_lab/NNR.pdf

http://www.ijdb.ehu.es/web/paper.php?doi=10668969


Modified model with 3 signals

https://www.ucl.ac.uk/cdb/research/stern/stern_lab/NNR.pdfl


Antagonism of Wnt signaling is important for head induction in frog embryos


Same story as before - Combinatorial expression of different genes specifies different areas

http://www.nature.com/nrn/journal/v4/n7/fig_tab/nrn1142_F6.html


Signaling center in the midbrain-hindbrain boundary organizes this region

● Homeodomain transcription factor engrailed expressed in the boundary

● This region has progenitors for midbrain (tectum) and cerebellum

● Chick-quail useful system for transplants


FGF8 is a critical signal for “organizer” activity

● FGF8 can induce entire second midbrain


Prosomeric model of forebrain development - Forebrain divided into grid of regional identities

● Transplants of neural tissue from host to donor

● Into different locations● At different time-points● What does this piece develop

into?● What about the neigbouring

regions?

● Several different transcription factors involved in specifying regions


Are there also master genes – Pax6 in eye development?

● Ectopic eyes can be induced by misexpressing Pax6 in other imaginal discs


Eye field induction in the anterior neural plate in vertebrates (Xenopus)

● Complex combination of transciption factors specify eye development


Dorso ventral axis in the developing neural tube set up by BMP and Shh

● BMP from the epidermis above sets up the roof plate as a signaling center

● Sonic hedgehog (Shh) from the notochord down below sets up the floor plate as a signaling center

http://www.nature.com/nrg/journal/v2/n8/fig_tab/nrg0801_620a_F2.html#figure-title


Differentiation in the neural tube is dependent on factors from adjacent non-neural tissues


Different genes expressed in different portions of developing spinal cord


Can be studied in cell-culture systems to identify molecules


Patterning of cerebral cortex – again, gradients of two transcription factors


FGF8 plays a role in patterning cerebral cortex


Assignment 1 – Poster on signaling pathways and mechanisms that contribute to patterning

● AP axis – forebrain, midbrain, hindbrain● DV axis – patterning of neural tube● Mesencephalon/metencephalon boundary● Hindbrain – hox genes● Cerebral cortex● Eye induction● Mammals, Drosophila, Chick, Frog, C-elegans

● Signaling pathways, Mechanisms, Key experiments, Outstanding questions

development of the nervous system – 2

Documents

development of nervous

neurobiology iaugust

specificity of hox genes

hox gene cluster

p axis hox genes

spatial order of hox

wellorganized hox clusters

vertebrate hox gene