Chapter 13- The neural crest

1. The neural crest Chapter 13- The neural crest Recall lineages Ectoderm-skin/nerves Mesoderm-Blood, heart, kidney, bones Endoderm- Gut and associated organs Recall- Ectoderm has three fates ___________(skin) 1._________ ____________________________ 2.Neural crest cells 3. _________ __________________ Fig. 12.3 This process is called ______________

2. The neural crest Neural crest cell fate depends largely on where they _______ The neural crest is a ________ structure Potential cell fates include- 1. _______ and _______ 2. ________ of adrenal gland (produces ___________) 3. ______________ cells of epidermis 4. Skeletal/connective tissue of ___________ Neural crest- four functional ____________ A. ___________- cartilage, bone, neurons, glia of face B. __________ C. ________- parasympathetic ganglia D. ________- melanocytes (produce pigment); sensory and sympathetic neurons, medulla Fig. 13.1

3. Sensory pathways- conduct info to brain-, spinal cord A quick review of nerve nomenclature 1. _____________ nervous system • “____________ controlled muscles”- • CNS sends signals to _______ muscles of heart, blood vessels, iris, pancreas liver, digestive tract, kidney • 1.___________- -homeostasis of body systems, originate from hindbrain • 2. ___________- fright and flight reactions- originate form spinal chord 2. ______ nervous system- -“__________ controlled organs”- - CNS sends signals to ________ muscles communication between various parts of the body (e.g. thallumus, cerebellum) with muscles Figure not in text

4. The neural crest Path 1-cells travel ______epidermis, become melanocytes, colonize hair and skin follicles Epidermis __________ __________ _________ This is a _______ A. Start with the _____Neural crest Two major paths taken Fig. 13.2 Path 2-cells to _____ of __________ and through anterior sclerotome to become sympathetic and sensory ________ Note – Sclerotome will become vertebral cartilage

5. The neural crest Neural Crest cells Ephrinin sclerotome How do these neural crest cells know where to migrate? 1. Epidermis secrete ____________________ - BMP-4 and –7 induce neural crest cells to produce slug and RhoB - Slug dissociates cell-cell tight junctions 2. ____________ expression is also lost then regained once reaching final destination 3. __________ proteins in extracellular matrix guide cells • Neural crest cells have Eph ___________ • Trunk sclerotome express Eph ________ • Binding of Eph receptor to Eph ligand interferes with migration • Thus, Eph proteins tell neural crest cells where _____to go Fig. 13.4 4. __________ factor allows continued proliferation 5. Other chemotactic and maintenance factors

6. The neural crest ________ Sympathetic and parasympathetic neurons ___________ Sensory neuron • Trunk neural crest cells are__________(can become many cell types) • However, it may be that only certain populations of cells are pluripotent • Some _________________ have been identified that dictate cell fate: Trunk neural crest cell ___________ recently shown to convert neural crest cells to sensory neurons in mice • Expose cells to Wnt1 - cells become sensory neurons • If do same experiment in B-cat -/- mice- no effect Lee et al, Science 303, 1020-1023 (Feb. 2004)

7. The neural crest Final cell fate is determined by final ______________ __________ Neuron Fig. 13.6- Fate of a trunk neural crest cell is influenced by _____ and ______________ FGF2 Glucocorticoids Neural crest Cell __________ Cell

8. The neural crest Rhombomeres B. The _________ neural crest Like the trunk neural crest cells, these can produce glia, ________ and _____________ But, only __________ neural crest cells can produce cartilage and bone • Recall – the neural tube subdivides into forebrain, midbrain and hindbrain • The hind brain then further subdivides into ________________ • Each rhombomere is a __________, each produces ganglia, but each has a distinct _____ • Rhombomeres sit behind the ________________ Pharyngeal arches Fig. 13.1

9. The neural crest Three paths for ________ neural crest cells: Rhombomeres in hind brain of ____________ Pharyngeal arches Incus, Malleus, jaw cartilege Stapes, Styloid Process 3. Rhombo. __ to 3rd and 4th Ph. Arch Hyoid bone, thyroid cartilage 1. Rhombomere ____- to 1st Ph. Arch 1 2. Rhombo. _- to 2nd Ph. Arch 2 3 4 Fig. 13.7 Rhombomeres _______ do not migrate through arches Fate map of pharyngial arches contributions to face formation

10. The neural crest + retinoic acid No ear WT Fig. 13.8 What determines distinct fates of cranial neural crest cells? Answer- The combination of ______ genes Evidence 1. _______KO- neural crest cells of 2nd Ph. Arch transformed into ___ Ph. Arch structures 2. Hoxa-1 and Hoxb-1 double KO- no _____________ migration • 3. Retinoic acid induces more ______ expression of certain Hox genes- • Induces rhombomeres 2 and 3 to assume role of rhombomeres _________

11. How is neuronal ______ achieved?? 5 ways- 1. Blocking ____ signal allows formation of dorsal neural tube (recall chapter 12) 2. __________ specifies _______ fate (not epidermal or glial) 3. Initial __________ determines neuronal type 4. Migration ___________ further dictates specificity 5. Specific _________ made with target organs or other neurons 3 parts described 1. __________ selection- axons travel along a given route 2. __________ selection- axons reach a target, then bind to specific cells 3. _________ selection- axons now refine interactions- bind to only a subset of possible targets

12. A. 5 Hypotheses for pathway selection- • _____________- Growth cone can adhere to certain cells, but not • others • ________ – a glycoprotein which appears to pave the road for several axonal migrations • ________ 2. _______________- Growth cone can adhere to certain cells, but not others 3. ____________ hypothesis- in ______, a neuron can precisely follow the path of a prior neuron Kallmann syndrome- an infertile man with lack of smell Reason- a single protein directs migration of both __________ axons and _______________ nerve cells • 4. ___________- • _______ (recall Fig 13.4) – Growth cones contain Eph _______- binding prevents migration into undesirable areas • ___________ proteins- important in directing axon turns

13. Fig. 13.20 Rat dorsal spine explant Neuron Outgrowth Neutrin producing cell Fig. 13.21 Sensory Neuron Motor Neuron Unc-6 -/- WT Hypotheses for pathway selection- (Cont.) 5. _______________- a. ____________ are chemotactic • Netrins are homologues of the ____________ in C. Elegans Loss of Unc-6 prevents migration of both sensory (to ventral) and motor (to dorsal) neurons b. _______________ are repulsive

14. B. Hypotheses for_________ selection- 0 min 2 min 6 min 10 min Target cells secrete short-range chemotactic or _____________ factors Example- NT-3 attracts axons C. Hypotheses for _______ selection- Fig. 13.24 Growth cone makes contact with a cell, ______________ receptors cluster on target cell surface, and a ______ is formed Additional axons synapse target cell, but eventually only _________ remains Fig. 13.25