MCDB 4777/5777 Molecular Neurobiology Lecture 29 Neural Development- In the beginning

Transcription

1 MCDB 4777/5777 Molecular Neurobiology Lecture 29 Neural Development- In the beginning

2 Learning Goals for Lecture Describe the contributions of early developmental events in the embryo to the formation and patterning of the nervous system. a. Relate the primary germ layers to their derivatives in the adult. b. Assess the impact of gastrulation, neurulation, and neural crest cell migration on the formation of the nervous system. c. Apply developmental concepts including cell fate, commitment, and differentiation; regional patterning; morphogenesis; and induction to events in nervous system development. 4.2 Explain how genes and their products interact in directing the differentiation of neurons. a. Summarize experimental evidence suggesting the default state of ectoderm is neural b. Describe the molecular signaling required for A/P and D/V regionalization of the neural tube c. Compare molecular mechanisms which can generate different types of neurons.

3 Overview of neural development 1- ectoderm -> neural 2- generation, migration of neurons and glia 3- specification of particular cell fates 4- axonal and dendritic pathfinding 5- formation of synaptic connections 6- activity-dependent competitive reorganization of connections 7- ongoing synaptic plasticity throughout life

4 Figure 22.1 Neurulation in the mammalian embryo (Part 1)

5 Figure 22.5 Regional specification of the developing brain

6 Figure 22.6 Sequential gene expression divides the embryo into regions and segments (Part 3)

7 Box 22E Rhombomeres (Part 2)

8 Box 22E Rhombomeres (Part 1)

9 Lecture 28 In which segments would you predict Hox genes alone can lead to different sets of mrnas being expressed? A. R3 and R4 B. R5 and R6 C. All of the above D. None of the above

10 Figure 22.1 Neurulation in the mammalian embryo (Part 1)

11 Patterning of the ectoderm by mesodermal signals Above is a Xenopus embryo sliced in half during gastrulation Note- arrows represent inductive signals from mesoderm to ectoderm responsible for creating and patterning neural tissue

12 21.3 Major inductive signaling pathways in vertebrate embryos. (Part 1)

13 21.3 Major inductive signaling pathways in vertebrate embryos. (Part 2)

14 21.3 Major inductive signaling pathways in vertebrate embryos. (Part 3)

15 Lecture 28 Have you seen these signaling pathways in an MCDB course before? A. FGF and Wnt only B. Shh andbmp/tgf beta (or one of these) only C. I ve seen more than one before D. I ve seen all of them E. I haven t seen any of them before

16 Ectoderm and Commitment- timing

17 Ectoderm and Commitment- not as simple as you might think

18 Figure 22.9 Mechanisms that guide neuronal and glial differentiation in neural ectoderm

19 Using the figures above, decide why the early isolated animal caps did not make neural cells. a. Chordin and noggin must be present in the early stage animal cap b. Chordin and noggin are not present in the early stage animal cap but BMPs are c. The animal cap cells can no longer be inhibited by BMPs after gastrulation d. The cells need to adhere to each other in order for BMPs to function

20 The spinal cord is organized by an interplay of dorsalizing and ventralizing molecules Dorsalizing molecules: BMPs in ectoderm and roof plate Dorsalin, Activin in dorsal NT 12.12

21 Lecture 28 What is the most interesting conclusion regarding specification of neural cell types that can be drawn from this figure? A. Specification of ectoderm to become nervous system tissue requires Shh B. The floorplate generates Shh C. Fates of neural tube cells depends on the concentration of Shh they receive D. Specification of Motor neurons requires signals from neighboring V3 and V2 cells E. None of the above

22 Shh is the morphogen responsible for ventral patterning Establishment of different classes of neurons depends on Shh concentration (motor neurons and V1-V3 are different classes of neurons)

23 Figure 22.9 Mechanisms that guide neuronal and glial differentiation in neural ectoderm

24 Figure 22.4 Local signals specify sensory relay neurons, interneurons, and motor neurons (Part 2)