Q 29 on Exam I: In the neural tube, BMP4 is to Shh as: a) Dpp is to Sog b) Engrailed is to Otx2 c) Hoxa2 is to retinoic acid d) Hes1 is to Hes5 e) Noggin is to BMP -Essentially, question was formulated to illustrate opposing DV gradients in development of the body axis & nerve cord/spinal cord. -I will give 2 pts to anyone who had points deducted from their grade IF they can provide a better answer to the question and clearly state the rationale for the alternative answer. In flies, dpp= BMP (blocks neural), & sog= noggin/chordin (promotes neural) Optional short presentations in class April 25th: -research a human neurological disorder and discuss in the context of developmental neurobiology -give a short 5-10 min slide presentation -write a 5-page report on how altered neural development may contribute/contributes to the disease, and which form of therapy you would recommend Examples: -Huntington’s chorea -Alzheimer’s disease -Major depressive disorder -Schizophrenia -Traumatic brain injury Retinal cell outgrowth on tectal membranes expressing EphrinA ligands: no temporal growth EphA2-/-; A5-/- RGCs randomly project to tectum; ectopic EphA3 R causes anterior shift of projections Gradients of both ligand (tectum) and receptor (axon) establish map Ephrins & EphR gradients shape the retinotectal map across species Retinal axon outgrowth is promoted at low levels of Ephrin-A2 Repulsive EphA signals guide retina N-T, tectum A-P axon mapping; attractive EphB signals guide D-V, D-V axon mapping EphrinA ligands activate EphA receptors, & EphrinBs activate EphB receptors High EphA (T ret) low EphrinA (A tect); high EphB (V ret) high EphrinB1 (M tect) EphrinB-EphB forward & reverse signaling in D-V retinotectal map The tectum/colliculus develops at the border between midbrain & hindbrain Grafting experiment demonstrates a midbrain-hindbrain organizer Fgf8: a potent signal within the MB-HB organizer Fgf8 bead duplicates the organizer region & mesencephalon in the diencephalon Olfactory receptor neurons synapse with 2nd order neurons in the glomerulus Each glomerulus in the olfactory bulb receives neurons of only one subtype Brain Nose Topographic map in the olfactory epithelium is random (grouped by odorant) Genetic labeling of an olfactory receptor revealed convergence on one glomerulus P2 receptor+ cells= blue Olfactory receptors are expressed on both dendrites and axons olfactory epithelium olfactory bulb (brain) Odorant receptor protein is expressed on both dendrites and axons of olfactory sensory neurons. A and B. Staining of mouse olfactory epithelium with antibodies to two different particular odorant receptors (one labelled in red, the other in green). C. and D. Staining of mouse olfactory bulb with the same antibodies. Scale bars, 10mm. (From Barnea et al., 2004) No defined regional specificity in the nasal epithelium for olfactory neuron subclasses The olfactory neuron subtype & glomerular target is defined by its receptor P2 receptor deletion causes loss of glomerular targeting Swapping M71 in place of the P2 receptor leads to glomerulus “X” targeting Other guidance factors are needed for precise glomerular targeting Fine-tuning synaptic connectivity: A) reducing # afferents/ arborization to multiple target cells Fine-tuning neural connectivity: B) removing redundant inputs (afferents) to the same target cell In maturing neural circuits: C) remove excess synapses on same neuron Synaptic maturation also involves altering # synapses from a specific presynaptic neuron (afferent projection) Dual innervation of muscle by motor neurons is lost postnatally Multiple innervations at the immature neuromuscular junction Electrophysiological test for number of convergent inputs *quantal increases in PSP amplitude estimate of input # The number of convergent innervations decreases with maturity