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

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

3. A quick review of nerve nomenclature 1. _____________ nervous system 2. ______ nervous system- Sensory pathways- conduct info to brain-, spinal cord -“____________ 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 Figure not in text -“__________ controlled organs”- - CNS sends signals to ________ muscles communication between various parts of the body (e.g. thallumus, cerebellum) with muscles

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

5. 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 Ephrinin sclerotome Neural Crest cells Fig. 13.4 4. __________ factor allows continued proliferation 5. Other chemotactic and maintenance factors The neural crest

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

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

8. B. The _________ neural crest 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 ________________ Fig. 13.1 Pharyngeal arches Rhombomeres

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

10. What determines distinct fates of cranial neural crest cells? Answer- The combination of ______ genes 1. _______ KO- neural crest cells of 2 nd Ph. Arch transformed into ___ Ph. Arch structures Evidence 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 _________ + retinoic acid WT Fig. 13.8 No ear The neural crest

11. How is neuronal ______ achieved?? 2. __________ specifies _______ fate (not epidermal or glial) 1. Blocking ____ signal allows formation of dorsal neural tube (recall chapter 12) 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 5 ways-

12. A. 5 Hypotheses for pathway selection- 1._____________- Growth cone can adhere to certain cells, but not others 2. _______________- Growth cone can adhere to certain cells, but not others ________ – a glycoprotein which appears to pave the road for several axonal migrations ________ 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. ___________- a._______ (recall Fig 13.4) – Growth cones contain Eph _______- binding prevents migration into undesirable areas b.___________ proteins- important in directing axon turns

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

14. B. Hypotheses for_________ selection- Target cells secrete short-range chemotactic or _____________ factors Example- NT-3 attracts axons 0 min2 min 6 min10 min Fig. 13.24 C. Hypotheses for _______ selection - 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