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Name _______KEY______________________ Nsci 4100: Development of the Nervous System 2015 Examination 1 Write your name on this page! On your bubble answer sheet, enter your name (last name first name) and your internet ID (X.500 name). Please do it now!!! Class 2 neuro 101 1. Which of the following cell types is NOT normally found in the brain? A. oligodendrocyte B. astrocyte C. Schwann cell D. microglia E. All of the above are found in the brain. 2. The major excitatory neurotransmitter in the central nervous system is … A. dopamine B. epinephrine C. ϒ-aminobutyric acid (GABA) D. glutamate E. seotonin 3. What ion is in higher concentration inside the cell than outside the cell in a neuron at rest? A. sodium (Na+) B. potassium (K+) C. chloride (Cl-) D. More than one of the above are correct. 4. Excitatory input to a neuron typically would … A. result in the membrane potential of the cell becoming more negative. B. result in the membrane potential of the cell becoming more positive. C. not result in a change in the membrane potential of the cell. Class 3 & 4 embryology 5. Neurons in the peripheral nervous system develop from what primary germ layer? A. mesoderm B. entoderm C. ectoderm D. More than one of the above are correct. 6. Which of the following statements is true regarding the neural crest? A. Schwann cells, sensory neurons and autonomic ganglion neurons develop directly from neural crest cells. B. Neural crest develops from cells between the alar plate and basal plate. C. Inhibiting BMP signaling in an early embryo would increase the number of neural crest cells. D. More than one of the above are correct. Nsci 4100 – Midterm Exam I page 2 7. Cells in which primary brain vesicle give rise to the pons? A. mesencephalon B. prosencephalon C. rhombencephalon D. myelencephalon E. More than one of the above are correct. Everyone received credit for #8 8. Cells in the outer layer of the optic cup in the early embryo will give rise to cells in what part of the adult eye? A. neural retina B. retinal pigment epithelium C. cornea D. lens E. More than one of the above are correct. 9. In the developing nervous system, all mitosis takes place at the ventricular surface of the neuroepithelium. True or false? A. true B. false 10. Neurons that synapse with the myofibers in the biceps muscle in your arm and can initiate muscle contraction developed from … A. neural crest B. cerebral cortex C. alar plate D. basal plate E. More than one of the above are correct. 11. In the brainstem, the column of neurons that connect to muscles derived from somites are found … A. ventrally near the midline. B. dorsally near the midline. C. laterally. D. in no consistent position along the length of the brainstem. Class 5 induction 12. In the frog embryo, the cells of the dorsal lip of the blastopore mostly will become … A. endoderm B. mesoderm C. skin D. nervous system E. More than one of the above are correct. 13. In a mouse embryo, with a knockout of the noggin, chordin and follistatin genes, you would expect to see more cells expressing Sox2 at the age at which the neural tube forms compared to a wildtype mouse. True or false? A. true B. false Nsci 4100 – Midterm Exam I page 3 14. Imagine that you cultured the animal cap from a frog embryo before the start of gastrulation. The animal cap was kept intact in culture. You added BMP4 to the culture medium at a high but physiological concentration. What fate would you predict most cells in your culture would acquire? A. neural tissue B. muscle C. skin D. alimentary (digestive) tract E. The cells would not differentiate. 15. In the experiment described in the previous question, what result would you expect if you introduced to all cells a morpholino to the SMAD that these cells normally express just prior to putting them in culture? A. neural tissue B. muscle C. skin D. alimentary (digestive) tract E. The cells would not differentiate. Class 6 & 7 regionalization (from Dr. Nakagawa) 16. Which of the following is NOT true about early regionalization? A. Inhibiting BMP signaling causes neural induction and the caudalization of the neural plate at the same time. B. The neural plate is prevented from taking on a caudal fate partly by Wnt inhibitors. C. Retinoic acid plays a role in caudalizing the early neural plate. D. -catenin and LEF/TCF transcription factors play a central role in Wnt-mediated gene regulation. E. More than one of the above are NOT true. 17. Which of the following is NOT true about the anterior-posterior patterning of Drosophila embryos? A. Many genes that are involved in anterior-posterior patterning of Drosophila embryos have homologues in vertebrate genomes and these vertebrate genes play roles in regionalization of their nervous system. B. A homeotic mutation results in one part of the body developing characteristics more typical of a different part of the body. C. Hox genes comprise a subset of homeobox genes. D. The striped pattern of expression of the pair-rule genes are a result of combinatorial gene regulation by upstream transcription factors. E. All of the above are TRUE. 18. Which of the following is NOT true about homeobox genes? A. Some homeobox genes are expressed in the forebrain and midbrain. B. They encode proteins that contain 60 amino acids of a conserved DNA-binding domain. C. Expression of homeobox genes is specific to the nervous system. D. Specific expression patterns of some homeobox genes form boundaries of progenitor domains in early embryonic nervous system. E. More than one of the above are NOT true. Nsci 4100 – Midterm Exam I page 4 19. The Dkk1 protein inhibits Wnt ligands from activating their receptors. What do you expect to observe in cells of the caudal neural plate when you place Dkk1-soaked beads in their vicinity? A. Increased amount of -catenin in the cell nucleus. B. Increased expression of genes that are normally expressed in more rostral parts of the neural plate. C. Transformation of the neural plate into an epidermal tissue. D. Increased expression of genes that are normally expressed in more lateral parts of the neural plate. E. None of the above is true. 20. When you use a chemical to induce random mutagenesis in fly germ cells, the same gene may be affected by different kinds of mutations and these mutations may cause very different outcomes. One mutation in the Antennapedia gene (Antp) in Drosophila results in ectopic antennae in the thorax (let’s call it “mutation 1”), whereas another mutation (“mutation 2”) results in ectopic legs in the head. It turns out Antp is normally expressed in the future thorax, but not in the future head, and the expression of Antp is lost in the thorax in mutation 1 and ectopically detected in the head in mutation 2. Which of the following statements better explains the phenotypes of the two mutations? A. Antp promotes the identity of the head and inhibits the identity of the thorax. B. Antp promotes the identity of the thorax and inhibits the identity of the head. 21. Which of the following is true about the anterior neural ridge? A. It produces Sonic hedgehog. B. It is formed at the interface between the neural plate and the notochord. C. It secretes molecules that inhibit expression of genes that are normally expressed in the rostral cerebral cortex. D. Removing it in the rostral neural plate results in the lack of telencephalon. E. None of the above is true. 22. Which of the following is true about rhombomeres? A. Each rhombomere expresses only one of the many Hox genes. B. Each rhombomere produces sensory neurons for a specific cranial nerve. C. Retinoic acid, via its receptors, directly regulates transcription of Hox genes in some rhombomeres. D. FGFs and retinoic acid are both expressed within the rhombomeres themselves. E. More than one of the above are correct. 23. The “cortical hem” is located in the caudal-medial part of the early embryonic cerebral cortex. It expresses several secreted signaling molecules including Wnt3a and BMP4. Which statement below is consistent with the hypothesis that Wnt3a is important in regional patterning of the cerebral cortex? A. Conditionally knocking out the Wnt3a gene in the cortical hem region will result in the shrinkage of the primary motor cortex. B. Ectopic expression of Frzb, a soluble Wnt inhibitor, in the caudal cortex will result in the increased expression of markers for the visual cortex. C. Axin2, a target gene of Wnt/β-catenin signaling, is highly expressed in the caudalmedial cerebral cortex. D. Grafting Wnt3a-expressing cells in the midbrain causes the formation of cerebral cortex there. E. None of the above is consistent. Nsci 4100 – Midterm Exam I page 5 Class 8 research (from Dr. Nakagawa) 24. Which of the following statements is true regarding the development of the thalamus? A. The rostral border of the embryonic thalamus produces BMPs but not Sonic hedgehog. B. Similar to the neocortex and the cerebellum, the thalamus is composed of six layers of neurons. C. Over-expression of a constitutively active form of the Smoothened protein in thalamic progenitor cells causes the same changes in patterning that were observed with the deletion of the Sonic Hedgehog gene in the diencephalon. D. The embryonic thalamus is composed of two distinct domains of neural progenitor cells. Class 9 & 10 cell division 25. At what phase of the cell cycle does cdk4 reach its peak level of expression? A. beginning of G1 B. beginning of G2 C. beginning of S D. beginning of M E. The concentration of cdk4 does not change appreciably during the cell cycle. 26. It has been suggested that the transcription factor Emx2 promotes symmetric cell divisions. If Emx2 was overexpressed in cortical progenitor cells in the early mouse embryo, what difference compared to controls would you expect to see later in development? A. a larger cortex B. a smaller cortex C. an increased percentage of deeper layer cortical neurons and reduction in superficial layer neurons D. an increased percentage of superficial layer cortical neurons and reduction in deeper layer neurons 27. Injecting BrdU into a pregnant mouse at the time at which the first cortical neurons are becoming postmitotic in the pups is likely to result in the pups later in development … A. having a larger cortex than normal. B. having deep layer cortical neurons labeled with BrdU. C. having superficial layer cortical neurons labeled with BrdU. D. having all cortical neurons labeled with BrdU. E. having cortical neurons only transiently labeled with BrdU. 28. Which of the following statements regarding the length of the cell cycle in the developing nervous system is true? A. The length of the entire cell cycle remains relatively constant in the neural tube until a cell ceases division and differentiates. B. The length of the cell cycle progressively increases as development progresses due primarily to an increase in the length of G1 phase. C. The length of the cell cycle progressively increases as development progresses due primarily to an increase in the length of G1 and G2 phases. D. The length of the cell cycle progressively increases as development progresses due primarily to an increase in the length of G1, G2 and S phases. E. The length of the cell cycle progressively decreases as development progresses due primarily to a decrease in the length of G1, G2 and S phases. Nsci 4100 – Midterm Exam I page 6 29. Retinoblastoma protein (Rb) normally … A. promotes cell division by activating E2F transcription factors. B. inhibits cells division by inactivating E2F transcription factors. C. promotes cell division by activating DNA polymerase. B. inhibits cells division by deactivating DNA polymerase. E. promotes cell division by inactivating cyclin dependent kinase inhibitor (CKI). 30. CyclinD is an enzyme that phosphorylates Rb. True or false? A. true B. false 31. Which of the following is true regarding cells with nuclei in the subventricular zone of the developing cerebral cortex? A. Some cells are postmitotic and are migrating through this layer on their way to the cortical plate. B. Some cells undergo division in this layer. C. Some cells begin to differentiate and grow out their axons in this layer. D. More than one of the above are correct. Class 11 & 12 cell migration 32. Cells in the neural tube migrate using … A. cilia. B. amoeboid movement. C. adhesion dependent crawling. D. bulk flow. E. More than one of the above are correct. 33. Injection of a short peptide fragment of fibronectin containing the RGD amino acid sequence into the mesoderm next to the neural tube in a chick embryo is likely to … A. increase neural crest cell migration. B. decrease neural crest cell migration. C. promote neural crest cell differentiation. D. increase skin pigmentation. 34. Each integrin … A. has three subunits, an α, a β and a γ subunit. B. has two subunits, an α and a β subunit. C. has two subunits, either two α or two β subunits. D. has two subunits that are dimerized and then internalized by ligand binding. E. More than one of the above are correct. 35. Migrating neural crest cells can be … A. attracted to a source of stromal cell-derived factor 1 (Sdf1). B. repelled by Cxcr4. C. repelled by Slit2. D. repelled by EphB3 AC E. More than one of the above are correct. Nsci 4100 – Midterm Exam I page 7 36. In the developing cerebellum … A. cells migrate from the pial surface towards the ventricle. B. cells migrate from the ventricular surface towards the pia. C. cells migrate from the midline towards the lateral side. D. cells migrate at random in all directions. AB E. More than one of the above are correct. 37. The excitatory neurons of the adult cortex are generated in the medial ganglionic eminence of the embryonic forebrain and undergo tangential migration into the cortex. True or false? A. True B. False 38. A mouse with the disabled (Dab1) gene knocked out has a disorganized cortex. Compared to wildtype cortex, what is the approximate sequence of the cortical cell layers in these mice (from pial surface to white matter)? A. 1, 6, 5, 4, 3, 2 B. 1, 2, 3, 4, 5, 6 C. 6, 5, 4, 3, 2, 1 D. 1, 2, 3, 6, 5, 4 Class 14 discussion 39. Which of the following is true regarding the developing neural tube? A. Shh signaling via activated Gli proteins directly promotes expression of cyclin D1. B. Wnt signaling via activated Gli proteins directly promotes expression of cyclin D1. C. Shh signaling via activated Gli proteins directly promotes expression of Wnt. D. Shh signaling is required for expression of Tcf3/4. E. More than one of the above are correct. Class 15 research (from Dr. Gammill) 40. Which of the following is NOT a true statement? Neural crest cells … A. migrate along defined pathways. B. give rise to structures called morpholinos that become structures in the face. C. are easily cultured by creating neural tube explants. D. have morphological and molecular similarities to metastatic cancer cells. E. arise in the dorsal neural tube, but can form non-neural cell types. The End! Please turn in this exam and your bubble sheet in the box at the back of the room. Double check that your name is on both.