1 / 29

Development of the Nervous System

Development of the Nervous System. Feb., 2014 Hugo J. Bellen Baylor College of Medicine/HHMI. Human Nervous System. The ‘ Seven Questions ’ of Neuronal Development. Neuronal Induction Neuronal Differentiation Neuronal Migration Axon Pathfinding Target Recognition Synapse Formation

nuru
Download Presentation

Development of the Nervous System

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Development of the Nervous System Feb., 2014 Hugo J. Bellen Baylor College of Medicine/HHMI

  2. Human Nervous System

  3. The ‘Seven Questions’ of Neuronal Development Neuronal Induction Neuronal Differentiation Neuronal Migration Axon Pathfinding Target Recognition Synapse Formation Synapse Elimination Etc….Synapse Maintenance/Aging/Plasticity

  4. Identifying genes that cause developmental defects is at the core of the success of studying nervous sytem development Forward genetics can be done in model organisms like worms and flies Identification of the genes then tells us something about the molecular mechanisms

  5. Why is information gained from animals relevant to human biology? • Genes encode the information for proteins, which are the building blocks of organisms • Genes are evolutionarily conserved: • striking parallels between flies and humans • amazing similarities between mice and humans • Once a system developed in an ancestral species, the building blocks (= proteins encoded by genes) are almost always maintained during evolution: e.g. muscle, nervous system)

  6. Evolutionary Conservation • Is much higher than previously thought • Has been confirmed in numerous ways including sequencing • Can be extremely informative to study and analyze biological processes across organisms • The basis for much of the success of biology in unraveling the mechanisms by which disease occur in the past 30 years

  7. Sensory organs of an adult Drosophila from Volker Hartenstein

  8. The VNC as a model • In each segment there are 60 neuroblasts, 30 on each side • They produce about 350 cells per hemisegment • Cell lineage is invariant for each neuroblast: this fate is acquired via positional information from the neurectoderm • The cartesian grid-like expression pattern repeats itself in each segment specifying the same sets of neuroblasts

  9. Patterning and specification of NBs • Patterns of proneural clusters and NB are identical. • Interaction of AP/DV gene activities specifies NB fates

  10. Peripheral senses in flies • Sight: eyes • Smell: olfactory receptors in antenna (nose) • Taste: taste receptors in labia and legs (tongue) • Hearing: Johnston organ in antenna (ear) • Proprioception: external sensory organs spread over body (skin)

  11. External sensory organs : a model to unravel the development of the PNS

  12. Proneural proteins and Notch signaling during sensory bristles development Lateral inhibition Asymmetric division

  13. Loss of Notch signaling results in aberrant bristle development Asymmetric division Lateral inhibition wild-type Loss of Notch

  14. pI pI pI IIa IIa so so so so Sensory lineage in WT and Notch mutations IIa IIb IIb IIb so sh st n n n n n wild-type loss of Notch gain of Notch

  15. Notch signaling regulates multiple processes during animal development in vertebrates • Cell fate decision: nervous system, blood, vasculature, pancreas • Asymmetric divisions: neurogenesis, myogenesis • Maintenance of undifferentiated state: hematopoietic, muscle and neural stem cells • Differentiation: skin, oligodendrocytes, bone

  16. General mechanisms of axon guidance Butler, S. J. et al. Development 2007;134:439-448

  17. Science 274, 1123 (96)

  18. Slit pathway:Slit, Robo, commissureless

  19. Keleman et al. (2002) Cell 110, 415 Model for Comm function (A and B) comm is the switch that controls midline crossing. In an ipsilateral neuron, comm is OFF. The growth cone carries high levels of Robo and is repelled by Slit. In a commissural neuron, comm is initially ON. Once the commissural growth cone reaches the other side, comm is turned OFF in order to increase Robo levels and prevent recrossing (B). (C) Comm regulates Robo trafficking. If comm is OFF, Robo is packaged into vesicles delivered to the growth cone. If comm is ON, most Robo is sorted by Comm into vesicles bound for late endosomes and lysosomes. Vesicles travelling to the growth cone thus contain very little Robo, and allows it to extend across the midline. LPSY motif is the Comm’s endosomal sorting signal. Keleman et al. (2005) Nature Neurosci. No evidence for Nedd4 function in midline crossing Myat et al. (2002). Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor. Neuron 35, 447-59.

More Related