Embr: signalling in development Flashcards
What is an inducer? what does it do?
An inducer is a population of cells or tissue that acts on another tissue (the responder) to stimulate a specific developmental pathway in the responding tissues
What signalling molecules are involved in induction?
Protein/peptide growth factors
what does the notochord become in adults?
nucleus pulposus in IV disk
Describe notochord formation
Area under the ectoderm thickens and a transient patterning structure is formed = notochord
What signals are released from the Notochord?
Chordin and Noggin
Describe the roles of Chordin and noggin in neural tube development
Noggin: inactivates BMP4. Absence of BMP4 causes patterning of neural tube and somites.
CHordin: BMP antagonist
Describe the formation and closure of the neural tube
Notochord sends signals to the overlying ectoderm to thicken and form the neural plate.
After the plate is induced, the neural plate lengthens
Lateral edges elevate to form the neural folds.
Depressed mid region forms the neural groove
The folds approach each other in the midline and fuse = NEURAL TUBE
Tube sinks in and overlying ectoderm repairs
What do cells of the neural plate make up?
Neuroectoderm
What are the last areas of the neural tube to close? when do they close?
Top and bottom
Anterior closes - day 25
Posterior closes - day 27
list the 3 mechanisms involved in ending the neural plate to form the neural tube? briefly describe two
Cells wedging - microtubules and microfilaments change shape
Hinge points
Extrinsic forces - pushing of surface ectoderm, adhesion with notochord
where does closure of the neural tube begins and how does it proceed?
Begin in the cervical region
proceeds in caudal and cephalic directions.
what are neuropores?
open ends of the neural tube
What is the role of SHH in neural tube folding?
Notochord releases SHH to the neural tube.
Ventral cells respond by making floor plate of the neural tube.
Once this is made, the floor plate can make its own SHH and is responsible for the development of motor neurons on each side of the neural tube
What is a neural tube defect?
Result of failure or incomplete closure of the neural tube
What is failure of anterior neuropore closure called?
Anencephaly
What is failure of posterior neuropore closure called?
Spina Bifida
In what region does Spina Bifida most commonly occur?
Dorsolateral region
what are the 2 types of hinge points? where are they ?
Median hinge point (where neural groove was)
Dorsolateral hinge point (to close the tube off)
Describe Spina Bifida occulta
less severe, hidden, vertebrae are not completely fused
Describe Spina Bifida cystica - meningocele
Sac protruding from spinal cord contains spinal fluid
Describe Spina Bifida myelomeningocele
Most severe, can result in paralysis or nerve root damage
what can help prevent spina bifida?
folic acid
raised levels of what protein can be used to diagnose SB?
Alpha-feto protein
what signalling molecule does SHH switch off?
noggin
In what area of the neural tube is the DLHP not needed? why?
Upper region - they come together easily themselves
What is needed to stop DLHP in the upper region
We want BMP2 to inhibit DLHP. So we need to switch off noggin so that it does not inhibit BMP 2. Need lots of SHH to switch off noggin.
In what area of the neural tube is the DLHP needed? why?
In the lower region as it is bigger and wider so needs help closing.
What is needed to keep DLHP in the upper region
We want DLHP, so need to inhibit BMP2. For this, we need noggin and low levels of SHH
How can SHH problems cause neural tube defects
High levels of SHH would mean no DLHP so can result in failure of closure of neural tube
what re the 2 genes needed in SHH signalling
patched and smoothened
Whats is the role of patched?
Patched is a negative regulator that inhibits smoothened. This blocks downstream signalling via Gli which would eventually transduce the SHH signal
What happens is SHH binds to patched?
It no longer inhibits smoothened, so smoothened can upregulate downstream signalling so Gli can bind to DNA and transduce the SHH signal.