Devo Lect 10 - Nervous system Flashcards
Main organs from ectoderm
Skin, pigment, brain and nerves, spinal cord
Main organs from mesoderm
Bones, connective tissue, muscle, heart and blood vessels
Main organs from endoderm
Gut epithelia, lungs, liver, pancreas
Hans Spemann experiment
Chimera study with two dorsal blastopores, one pigmented; formed 2nd invagination, basically formed two bodies, one not pigmented except in neural tissue; transplanted section called the organizer
Organizer
dorsal lip of the blastopore in amphibians; Initiates gastrulation, determines orientation; brain/neural tube forms first
Inductive events to form nervous system
Formation of mesoderm: endoderm induces ectoderm to become mesoderm; chordamesoderm; endoderm releases activin; form neuroectoderm
Chordamesoderm
Part of mesoderm which gets exposed to highest [activin], alters fate to form notochord
What is activin?
Growth factor that activates transduction pathway; paracrine effect from endoderm to form mesoderm by binding to receptors on ectoderm cells at specific time
Activin experiment
Add low concentration (.1ng/mL )forms bloodlike cells, mesenchyme; 1ng/mL forms muscle cells; 10ng/mL forms notochord; 100ng/mL forms heart muscle cells
What receptor type does activin bind to?
Receptor with 3 regions (binding, transmembrane, kinase)
Describe two engineered activin receptors
ActRIIBexd didn’t have an inner or transmembrane domain, freefloating. ActRIIBdn is dominant negative without kinase domain only. These are in high concentration, so they compete for activin.
How did injection of ActRIIBexd affect levels of expression of Xbra? What is Xbra?
Xbra is mesodermal marker. The exd receptor blocks activin specifically, so the early expression of Xbra is delayed by about one stage, so development is abnormal (esp. anterior)
Rescuing activin experiment
Injected activin mRNA, activin released and acts autocrine by binding to the normal receptors after saturating the truncated ones, higher does almost completely rescues
Formation of neuroectoderm
Chordamesoderm induces cells of inner ectoderm to become neuroectoderm; this forms the neural plate, which folds to form neural tube
Cell adhesion around neural tube
Epidermis has E-cadherins; neural tube cells change adhesins to N-Cad and N-CAM to fuse; neural crest cells have no adhesins
Neurula embryo
An embryo that has formed the neural tube
What is the first organ to form
Neural tube. Not functional yet, but still organ.
Chordin, noggin
Molecules released from chordamesoderm which induce formation of neuroectoderm; are not GF; they alter function of growth factors by binding to them, ie growth factor antagonists (block BMP)
BMP
bone morphogenic proteins; important cytokines in morphogenesis (originally discovered in bone and cartilage development)
Chordin, noggin knockouts
If one of them knocked out: fairly normal, ears are a bit different; both knocked out: very abnormal, one eye, forebrain quite irregular; show synergy, genetic redundancy
Human nervous system development**
Day 19: neural plate and chordamesoderm; D 21 (stage 9): invagination, placenta functioning; D22: neural tube, somites; D23 (stage 10): neuropores; D24: Ant. neuropore closed; D26: post. closed; D27 (stage 12): 3-5mm, pharyngeal arches, limb buds, brain forming, connecting stock (umbilical cord)
Neuropores
Ant. and Post., openings of neural tube at stage 10. Ant. closes at D24, if not results in anencephaly; Post. closes at D26, if not results in spina bifida (need folic acid)
Somites
Clumps of mesoderm tissue near neural tube; form the vertebrae
Day of development and stages of development
Organisms develop at different rates, so we compare the stages (Carnegie stages)
