Chapter 5 Genetics and the Development of the Human Brain OUTLINE Genetics Neurodevelopment Genetics Science of genetics explains the diversity of species upon which natural selection operates Humans have 23 matched pairs of chromosomes with each parent contributing one chromosome Humans Have 23 Pairs of Chromosomes Major Principles of Genetics Genes are sequences of nucleotides that code for specific amino acids which when strung together make a protein Humans estimated to have 23 000 protein coding genes Major Principles of Genetics Genes are sequences of nucleotides that code for specific amino acids which when strung together make a protein Humans estimated to have 23 000 protein coding genes Alternative versions of a gene called an allele may be dominant or recessive Combinations of Alleles Lead to Different Traits Blood Type Sources of Genetic Diversity Meiosis chromosomes in the eggs or sperm can be shuffled in over 8 million combinations Crossing over equivalent segments of DNA are exchanged unique gene combinations Meiosis 223 8 388 608 possible Crossing Over Sources of Genetic Diversity Meiosis chromosomes in the eggs or sperm can be shuffled in over 8 million combinations Crossing over equivalent segments of DNA are exchanged unique gene combinations Mutations may occur spontaneously or in response to exposure to radiation chemicals or other mutagens Thalidomide Biophoto Associates Photo Researchers Traits controlled by genes on the X chromosome occur more frequently in one sex than the other If dominant occurs more frequently in females 2 Xs If recessive occurs more frequently in males 1 X Photo Researchers Biophoto Associates The Special Case of Sex Chromosomes Biophoto Associates Photo Researchers Sex linked characteristics recessive genes on one X chromosome that are not duplicated on the Y chromosome will be expressed in male offspring Photo Researchers Biophoto Associates The Special Case of Sex Chromosomes Biophoto Associates Photo Researchers X chromosome inactivation the random inactivation of half the genes on the X chromosome in each cell of a female organism prevents the production of excess amounts of protein Photo Researchers Biophoto Associates The Special Case of Sex Chromosomes Sources of Genetic Diversity Meiosis chromosomes in the eggs or sperm can be shuffled in over 8 million combinations Crossing over equivalent segments of DNA are exchanged unique gene combinations Mutations may occur Single Nucleotide Polymorphisms SNPs Alleles that differ in only a single nucleotide Affect protein function and can influence some diseases Single Nucleotide Polymorphism APOE gene located on chromosome 19 has three alleles variants The APOE SNP predicts a person s risk for developing Alzheimer s disease OUTLINE Genetics Neurodevelopment Fertilization Zygote cell formed by the merger of egg and sperm Early Development Within the 1st week following conception the human zygote has divided into three germ layers Ectoderm nervous system skin hair Mesoderm connective tissue muscle bone blood vessels Endoderm internal organs Early Development Within the 1st week following conception the human zygote has divided into three germ layers Ectoderm nervous system skin hair Mesoderm connective tissue muscle bone blood vessels Endoderm internal organs Beginning around the 2nd week following conception the zygote is referred to as an embryo During the 3rd week following conception inducing factors differentiate the ectoderm layer into skin and neural plate The developing neural plate forms the neural tube Tube itself forms ventricular system of the brain and central canal of the spinal cod Surrounding tissue brain and spinal cord Closing of the Neural Tube Neural tube forms ventricles central canal of spinal cord Surrounding tissue becomes brain and spinal cord Early Development By the end of the 8th week the human embryo shows rudimentary beginnings of most body organs After 10th week the developing human is called a fetus Overview of Neural Development 1 Cell proliferation Neurogenesis generation of new neurons Gliogenesis generation of new glia 2 Migration 3 Differentiation 4 Circuit Formation Axon Growth Synaptogenesis 5 Neuron Death Apoptosis 6 Refinement of connections Synaptic pruning Embryonic Stem Cell Totipotent ability to develop into any type of cell in the body Unlimited capacity for self renewal Neural Stem Cell Pluripotent ability to develop into many types of mature nervous system cells Unlimited capacity for self renewal Neural Progenitor Cell Unipotent or oligopotent ability to develop into one or a few types of mature nervous system cells Limited capacity for self renewal Step 1 Cell Proliferation New neural cells are produced from the mitosis of progenitor cells in the ventricular zone lining the neural tube Some daughter cells remain in the ventricular zone and keep dividing Other daughter cells migrate away from the ventricular zone Step 2 Migration Step 2 Migration Step 3 Differentiation The neural tube differentiates in two directions Rostral caudal anterior posterior spinal cord hindbrain midbrain forebrain Dorsal ventral Dorsal half sensory neurons BMP Dorsal root in spinal cord Ventral half motor neurons Sonic hedgehog Ventral root in spinal cord Step 4 Circuit Formation Axons grow toward target cells and form synapses Growth cones sample environment for directional cues Filopodia and lamellipodia pull growing branch behind them Filopodia Lamellipodia Growth Cones Respond to Chemical Cues Chemoattractant Chemorepellant Axons growing in same direction stick together process called Fasciculation Cell adhesion molecules cause axons to stick together Step 4 Circuit formation Synaptogenesis Once axons reach their destination they must establish new synapses i e synaptogenesis Step 5 Cell Death Significant numbers of new neurons die during development in a process called apoptosis Target cells produced limited quantities of neurotrophins e g NGF Advancing axons compete for neurotrophic factors NGF promotes survival by inhibiting caspase activity Cell death genes Activate Caspases Breakup DNA Proteins Cell Death Step 6 Synaptic Pruning Synapses follow a similar pattern of overproduction followed by pruning Synapse density over time Step 6 Synaptic Pruning Synapses follow a similar pattern of overproduction followed by pruning Number of synapses in visual cortex peaks at 1 year of age Step 6 Synaptic Rearrangement Synapses not joined to functional neural