Brain regions Dorsal on the back vs ventral on the chest side Anterior towards the head vs posterior at the end tail Rostral anterior vs caudal posterior Forebrain prosencephalon paired cerebral hemispheres telencephalon diencephalon o Diencephalon thalamus hypothalamus optic vesicles Midbrain mesencephalon midbrain structures o Grows proportionally less compared to prosencephalon Hindbrain rhombencephalon metencephalon myelencephalon o Metencephalon cerebellum o Myelencephalon medulla pons o Eating breathing survival mechanisms o Rhombomeres repeated units all have same identity at first but then must differentiate 3 hox genes expressed in more anterior rhombomeres and more 5 genes expressed in more posterior rhombomeres Deletion of all hox gene expression by deleting pbx a transcription factor required fr gene expression leads to default state rhombomere 1 1 is default builds upon that They removed hoxa 1 gene removed from hindbrain miss things coming from rhombomeres 4 and 5 Spinal cord o Stems from posterior hindbrain Neural crest cells o Arise from dorsal spinal cord epidermis boundary and migrate down o dorsal root ganglia skin pigments all nervous system outside CNS parasympathetic ganglia And their adult derivatives see figure 5 Hypotheses theories organizers phrases Animal models o Xenopus laevis Xenopus African clawed frog Advantages large eggs embryo many eggs easy maintenance relatively resistant to disease slow external development English scientist Hogben discovered use of them for pregnancy test in South Africa became widely used model Disadvantage triploid o Xenopus tropicalis trops replaced Xenopus because more convenient o C elegans worm one of simplest organisms with nervous system Advantages small transparent feeds on bacteria easy housing short life cycle 959 cells exact cell lineage known 302 neurons 56 glial cells Common lineage between skin and nervous system both from ectoderm o Drosophila fruit fly see figure 2 Shared lineage of ectoderm conserved involution of cells Great for studying genetics widely used o Danio Rerio Zebrafish Advantages easy care vertebrate external development easy to generate many embryos complete cell lineage known transparent Zebrafish cells sit on top of yolk and start to divide then migrate down over the yolk doesn t exactly involute the same way but rather goes down and around and then involutes into the same layers o Gallus domesticus chick Looks different from humans but fundamentally similar Hensen s node at top analogous to dorsal lip of blastopore Default model of neural differentiation o Default fate of ectoderm is to become neural o Neural differentiation is being repressed in the ectoderm dorsal to the blastopore by something secreted from the underlying mesoderm Spemann s organizer experiment o Saw that gastrulation is when cells become committed o Grafted dorsal lip of blastopore involuting zone to anterior part of host embryo formation of new body axis Siamese twins track cell lineage through lineage labeling label them early on to see where they ended up found that grafted tissue induced host cells to turn into nervous system o Dorsal lip can organize entire embryo and induce neural tissue that wouldn t normally be neural tissue Spemann Organizer o Lithium chloride increases Spemann s organizer activity Ectoderm mesoderm endoderm and derivatives o Endoderm inner layer of embryo digestive tube and associated o Ectoderm outer layer of embryo surface layer of skin epidermis organs including lungs and nervous system o Mesoderm middle layer comes from IMZ blood heart kidney gonads bones connective tissue Signal transduction transmission of signal from cell exterior to interior o Signal reception transduction response o Most act in similar manner ligand binds receptor Smad complex is activated turns on a gene o Ex BMP and wnt pathways o Blocking signal transduction molecular equivalent of cutting Waddington landscape 1957 Neural cells diverge by the progressive narrowing of potential fates as development progresses Gastrulation see figure 1 o Start with zygote fertilized egg Early cell division cleavage blastomere divides some more and becomes a pluripotent mass of cells called a blastula Rearrangement of these cells into primary germ layers gastrulation o Blastopore hole in embryo o Involution begins dorsally o Humans similar gastrulation to chicks flattens out migration in No yolk obvious vegetal pole After gastrulation cells start to differentiate Waddington landscape neural cells diverge by the progressive narrowing of potential fates as development progresses o The blastula is pluripotent and could potentially become any all parts of the organism Imagine it rolling down a mountain that breaks off into different troughs once it goes down one path it can t easily go back up or switch paths The deeper it goes the deeper the crevice of the mountain aka the harder it is to change fates o Waddington started to explore how cells go from pluripotent stem cells to specialized differentiated ones and how that fate is much easier to switch earlier on in development Zygote fertilized egg Blastula pluripotent mass of cells stem cells that could differentiate into anything Hensen s node forms Dorsal lip of blastopore o Analogous to dorsal lip of blastopore o Organizing center at top where cells are involuting where neural tissue o Spemann organizer can induce neural tissue where it normally doesn t grow organizes the body axis o grey crescent formation necessary for neural tissue to arise o Candidate molecule induces an organizer induces neural tissue Neural induction indirect model o Candidate molecule added into solution being cultured with animal cap and directly induces neural tissue direct model IMZ involuting marginal zone on blastula that involutes and becomes mesoderm o Gives rise to mesoderm o Cutting experiment Take out IMZ animal cap pre gastrulation becomes epidermis Take out IMZ post gastrulation becomes neural tissue o This area expresses BMP inhibitors Co linearity o Where it is in the chromosome is lined up with where it is in the body spatial co linearity o There s also temporal co linearity most 3 gene also expressed first Response elements o Upstream of the gene where the receptor can bind Activator transformer hypothesis o Two signal model of neural patterning First a signal from the dorsal mesoderm organizer a induces the overlying ectoderm to become neuroectoderm of anterior character activation step