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Neural Development • How does a single cell make a brain??? • How are different brain regions specified??? 1 Neural Development • How do nerve become nerve cells? – Environmental factors • Inductive events • 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 Determination: A cell is restricted in its developmental potential. Differentiation: Cell elaborates a specific developmental program. 3 Complexity of the human brain 100,000,000,000 neurons Each neuron makes 1000 synapses Regional specializations 4 Major Processes in Development egg 1n + 1n zygote = 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 5 Initial Steps in the Development of the Nervous System: Fertilization Cleavage Gastrulation Neurulation 6 Looking at early development of the nervous system: Xenopus Frog 7 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 8 movie 9 Early events in neural development Gastrulation Neurulation 10 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. 11 Long After Neurulation: Neural Crest Neural Tube Rostral Brain Caudal Spinal Cord PNS (sensory ganglia, ANS), melanocytes, adrenal medula 12 - How do ectodermal cells become neural cells? - How is polarity established? Dorsal Ventral ? 13 Early events in neural development Gastrulation Neurulation 14 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 15 16 The organizer region is responsible for converting ectoderm into neural cells Model: Inductive signal in dorsal lip instructs ectoderm 17 The organizer region is responsible for converting ectoderm into neural cells early late MODEL: Organizer has instructed cells to become neural 18 How does the organizer instruct epidermal cells? Experiment 1: Neurons can form in the absence of the organizer The default is to become neural Model: Epidermis makes local signal that inhibits neural fate 19 How does the organizer instruct epidermal cells? Experiment 2: 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 20 Activation of BMP signaling inhibits the neural fate NOT NEURAL 21 How does the organizer instruct epidermal cells? Experiment 3: Same idea as 2: Inject blastocyst with genes from the organizer and see if any cause the animal cap to become neural Neural fate (?) Take the animal cap Inject mRNAs Noggin is a secreted protein, expressed in the organizer and later in the notocord. Noggin inhibits BMP signaling. Follistatin and chordin have similar functions. 22 Inhibition of BMP signaling makes cells adopt neural fate == NOGGIN NEURAL 23 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 24 Model: The ‘double inhibition model’ for neural fate 25 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) 26