Neural Development. How does a single cell make a brain??? How are different brain regions specified??? Neural Development

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1 Neural Development How does a single cell make a brain??? How are different brain regions specified??? 1 Neural Development How do cells become neurons? Environmental factors Positional cues Genetic factors Competence Cell lineage Timing 2 Neural Development depends on genes and environment Keywords in Development Induction: Cells are instructed to adopt a fate by signals in the environment. Competence: the ability of a cell to respond to a signal. It depends on the receptors, transcription factors, etc expressed by the cell. Differentiation: Cell elaborates a specific developmental program. Determination: A cell is restricted in its developmental potential. 3 1

2 Major Processes in Development egg 1n + 1n = embryo 2n 1. Mitosis -cell division 2. Patterning -cells are arranged in proper positions -the body plan is established 3. Differentiation -cells become different from each other -they acquire specific functions 4 Initial Steps in the Development of the Nervous System: Fertilization Cleavage Gastrulation Neurulation 5 Looking at early development of the nervous system: Xenopus Frog Cleavage Fertilization Gastrulation Neurulation 6 2

3 Early events in neural development Gastrulation : Gastrulation is the process by which the embryo acquires 3 germ layers. There is intense cell movement and rearrangement Ectoderm Major tissues of the Nervous System, Epidermis Mesoderm Connective Tissue, Muscle, Vessels Endoderm guts, lungs, liver 7 movie 8 Early events in neural development Gastrulation Neurulation 9 3

4 Neurulation: Formation of the Neural Tube After Gastrulation comes Neurulation. During Neurulation, the neural plate invaginates, and the neural folds close to form the neural tube. 10 Long After Neurulation: Rostral Brain Neural Tube Caudal Spinal Cord Neural Crest PNS (sensory ganglia, ANS), melanocytes, adrenal medula 11 - How do cells become neurons?? 12 4

5 Early events in neural development Gastrulation Neurulation 13 Classic experiment showing the induction of the nervous system Hans Spemann discovered the organizer----nobel 1935 Expt: Transplant different parts of the developing embryo (donor) into another embryo (host) Result: 1) If the dorsal lip is transplanted, a second embryonic axis forms 2) The second embryo has both host and donor tissue

6 The organizer region is responsible for converting ectoderm into neural cells Model: Inductive signal in dorsal lip instructs ectoderm 16 How does the organizer instruct epidermal cells? Experiment: Dissociate animal cap, grow in culture Result: Neurons can form in the absence of the organizer The default is to become neural Model: Epidermis makes local signal that inhibits neural fate 17 How does the organizer instruct epidermal cells? Experiment: Inject blastula with genes of interest. Do any cause animal cap to become neural? Result: Expression of a dominant negative mutant of a BMP receptor results in neural fate. Model: BMP signal instructs cells not to become neural 18 6

7 Activation of BMP signaling inhibits the neural fate BMP signaling: receptor serine kinase NOT NEURAL 19 How does the organizer instruct epidermal cells? Experiment: Inject blastocyst with genes from the organizer and see if any cause the animal cap to become neural Inject mrnas Take the animal cap Neural fate (?) Noggin is a secreted protein, expressed in the organizer and later in the notocord. Noggin inhibits BMP signaling. Follistatin and chordin have similar functions. 20 Inhibition of BMP signaling makes cells adopt neural fate == NOGGIN NEURAL 21 7

8 Current Model for how cells become neural 1) Default state is neural 2) Local secretion of BMPs by epidermis inhibits neural fate 3) Local secretion of noggin, chordin by dorsal lip or mesoderm inhibits BMP signaling 4) Inhibition of BMP signaling give rise to neural fate Double Inhibition Model for Neural fate 22 Model: The double inhibition model for neural fate 23 A cell s fate will depend on the signals to which it is exposed as well as the developmental history of the cell (which genes they express) 24 8