Bio 127 - Section III Organogenesis

1. Bio 127 - Section IIIOrganogenesis The Neural Crest and Axonal Specification Gilbert 9e – Chapter 10

2. Student Learning Objectives • You should understand that the neural crest is an evolutionary advancement unique to vertebrates. a. Led to jaws, face, skull, sensory neural ganglia b. Transient structure: exists briefly at neural tube closure 2. You should understand that the neural crest is specified into four overlapping regions along the anterior-posterior axis: a. Cranial neural crest b. Cardiac neural crest c. Trunk neural crest d. Vagosacral neural crest

3. Student Learning Objectives 3. You should understand that most cells of the neural crest are either multipotent progenitor cells or are already determined to a fate. a. Large majority of early chick cranial NC can form all cranial fates but only ~10 of the total population that migrates out. b. Nearly half of chick trunk NC are restricted to one fate c. Other cells from chick trunk NC can produce: 1. sensory neurons 2. melanocytes 3. adrenomedullary cells 4. glia 4. You should understand that it is unknown if any NC population is a true stem cell, capable of generating stem cells or multiple progenitors

4. Around the time of neural tube closure... Neural crest cells migrate laterally and ventrally from the dorsal side of the tube.

5. Usually the migration is a ‘fire drill’ and all cells leave the a tube... Distances can vary from short to very long migrations.

6. Anterior-Posterior patterning of tube extends to the crest Cranial NC • Vagosacral NC Cardiac NC Vagal NC Trunk NC Sacral NC

7. Neural Crest Cell Fates

8. Anterior-Posterior patterning of tube extends to the crest Your starting position limits (specifies) your fate choices and your experiences on the road choose (determine) the one.

9. Figure 10.17 The influence of mesoderm and ectoderm on the axial identity of cranial neural crest cells and the role of Hoxa2 in regulating second-arch morphogenesis

10. Figure 10.10 Cranial neural crest cell migration in the mammalian head

11. Cranial Neural Crest

12. Cardiac neural crest Pax3 in outflow tract arteries Contribution to cardiac septum

13. Cardiac Neural Crest

14. The Trunk Neural Crest The cells of the Trunk NC can head off one of two directions (the other is the ventral pathway)

15. Trunk neural crest cell migration Some individual cells can contribute to multiple fates

16. Trunk Neural Crest

17. Ventrolateral cell migration through anterior sclerotome only

18. Restriction due to the ephrin proteins of the sclerotome

19. Anterior-Posterior patterning of tube extends to the crest Cranial NC • Vagosacral NC Cardiac NC Vagal NC Trunk NC Sacral NC

20. Vagosacral Neural Crest

21. Figure 10.8 Entry of neural crest cells into the gut and adrenal gland

22. Figure 10.18 Plasticity and pre-patterning of the neural crest both play roles in beak morphology

23. Neuronal Specification and Axonal Specificity • 100 billion neurons in the adult • 300 billion born! • All with a single axon, one or a few synapses • All with a single phenotype, neurotransmitter • Making the right synapse is critical • Motor neurons better find a skeletal muscle • Retinal neurons better find the optic tectum

24. Neuronal Specification and Axonal Specificity • Induction and patterning of brain region • Birth and migration of neurons and glia • Specification of cell fates • Guidance of axons to specific targets • Formation of synaptic connections • Competitive rearrangement of synapses • Survival and final differentiation by signal • Continued plasticity throughout life

25. Heirarchical Specification ectoderm blocking BMP epidermis neural crest neuroepithelium Delta-Notch neuron glia ependyma Shh/TGF-B motor sensory interneuron Hox genes jaw forelimb hindlimb tail

26. Heirarchical Specification hindlimb birthday retinoic acid columns of terni (CT) medial motor columns (MMC) lateral motor columns (LMC) Lhx-3 TF cadherins Lim family TF axial muscles express FGF-R positive chemotaxis lateral subdivision medial subdivision Isl-2, Lim-1 express Eph-A4 repelled by ephrin-A5 forces them into hamstring Isl-1, Isl-2 express neuropilin-2 repelled by semaphorin-3F forces them quadriceps

27. Guidance of Axons to Specific Targets signals in the membranes of cells along the migratory path

28. Guidance of Axons to Specific Targets Ephrins and semaphorins can cause the growth cone to collapse semaphorin 3 expressing cells semaphorin 3 expressing cells

29. Guidance of Axons to Specific Targets guidance of the growth cone

30. Guidance of Axons to Specific Targets Netrin is a secreted chemotactic signal for axons Remember DSCAM? 38,016 splice variants in Drosophila

31. Guidance of Axons to Specific Targets Few neuronal axons cross the midline of the CNS creating the hemispheres Robo-3 overcomes Robo-1 Slit is secreted Robo-1 is repelled

32. Guidance of Axons to Specific Targets BMPs are secreted from targets, different BMP receptors guide branches to different targets

33. Formation of Synaptic Connections Reciprocal induction Requires synaptic transmission

34. Formation of Synaptic Connections Multiple axons compete for final innervation

35. Survival and final differentiation by signal • Apoptosis is often a dominant influence • More than half of the neurons may die regionally, two-thirds of the total born! • This is less consistent across species than most neural development events • 80% of cat retinal ganglion cells die • 40% in chick • 0% in fish, amphibians

36. Survival and final differentiation by signal • Neurotrophic factors block default apoptosis • Huntington’s corea is a loss of Huntingtin protein which upregulates BDNF and the survival of striatum neurons • coordinate movement, balance, walking • Parkinson’s disease is death of dopaminergic neurons which respond to GDNF and CDNF – therapy?

37. Continued plasticity throughout life • Many organisms have behaviors before birth • We can alter synaptic connections thru life • Less so when we get older