Sanes Chapter 3 questions - elsevier.com€¦ · Web viewSynthesis phase. G2 phase. Mitosis phase...

Sanes Chapter 3 questions

[1] Because there are many more glial cells than neurons in the human brain, glial cells tend to not migrate from the point of origin to their final position during histogenesis.

a. Trueb. False*

[2] Mechanisms controlling the number of neurons and glia

a. Do not include a limitation on progenitor cell divisionsb. Include extracellularsignals, acting as mitogens, to prevent cell deathc. Cell death of mature neurons and glia*d. All of these are true

[3] Histogenesis in C. elegans and drosophila is largely stereotyped and can be predicted from the lineages of the progenitor cells.

a. True*b. False

[4] During early neurogenesis in the vertebrate neural tube, daughters of progenitor cells move from the inner to outer surfaces of the neural tube in a process called

a. Interkinetic nuclear migration*b. Pre-mitotic nuclear migrationc. Post-mitotic nuclear migrationd. Vitreal-apical nuclear migration

[5] During mitosis, progenitor cells in the neural tube go through two phases

a. An S-phase and an M-phase of about equal durationb. An S-phase which is much shorter than the M-phasec. An M-phase which is much shorter than the S-phase*d. An M-phase and an S-phase of variable durations

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[6] Retroviral labeling

a. Is used to track the migration neuron and glial cellsb. Is also called “clonal analysis” c. Relies on the inability of a retrovirus to infect cells other than the originally

infected progenitors.d. All of these are correct*

[7] Modifying a viral genome to encode, for example, green fluorescent protein, makes it possible to identify the ultimate location of oligodendrocytes or astrocytes that have migrated away from the neural tube.

a. True*b. False

[8] The term “multipotent progenitors” refers to the fact that progenitor cells

a. May produce many different types of neuronsb. May produce motor neurons and astrocytesc. May produce neurons and macroglia*d. May produce neurons and oligodendrocytes

[9] In addition to the retroviral method for tracking progeny of progenitors, the classic technique is called

a. H-thymidine birthdating*b. Interkinetic nuclear migrationc. Green fluorescent protein stainingd. Clonal analysis

[10] Frequently used means for identifying labeled daughter cells include

a. Detection of antibodiesb. Immunofluorescencec. Autoradiographyd. All of these*

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[11] Entire populations of one type of neuron, such as spinal motor neurons, become post-mitotic over the whole period of neurogenesis.

a. Trueb. False*

[12] The rule “larger first” means that pyramidal cells become post-mitotic before hippocampal granule cells and in the cerebellum, Purkinje cells are generated before granule cells.

a. True*b. False

[13] The overall maturational pattern of histogenesis in the mammalian cerebral cortex as determined by autoradiography (rat) is

a. Inside out*b. Outside inc. Regionally specificd. Motor before sensory

[14] Maturational patterns of neuronal generation seem consistent with the hypothesis that phylogenetically older parts of the brain develop before the more recently evolved structures.

a. True*b. False

[15] The h-thymidine method has shown that the overall length of the progenitor cell cycle increases during embryogenesis; what increases the most is the

a. G1 phase*b. Synthesis phasec. G2 phased. Mitosis phase

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[16] Retroviral infections of progenitor cells in the early embryonic brain produces few clones than the same infections in late-staged embryos

a. Trueb. False*

[17] In later stages of histogenesis, when cell divisions are no longer symmetric, a greater and greater proportion of progenitor cells differentiate into

a. Neuronsb. Gliac. Either neurons or glia*d. multipotent progenitor cells

[18] The molecular mechanisms that control the proliferation of progenitors in the nervous system are similar to those that control cell division in other tissues from simple eukaryotic cells to complex animals and plants.

a. True*b. False

[19] The progenitor pool is depleted a. At the end of the expansion phase (high Q fraction)b. At the beginning of the expansion phase (low Q fraction)c. At the beginning of the neurogenic phase (low Q fraction)d. At the end of the neurogenic phase (high Q fraction)*

[20] The protein retinoblastoma (Rb) inhibits cells from passing from the G1 phase into the S phase; inhibiting this braking mechanism is accomplished by

a. cyclinD/cdk4 phosphorylates Rb, releasing transcription factor E2F which activates genes that push the cell into the S-phase*

b. cyclinD binds to Cdc2, which forms an active complex that suppresses Rb and pushes the cell into the S-phase

c. Mitogens like EGF and FGF stimulate Rb and cdki(p27) expression, which in turn stimulates the cell to enter into the S-phase

d. cycB and cdk2 inhibit the expression of Rb, allowing the cell to enter the S-phase

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[21] The Rb a. gene was the first of a class of tumor suppressors to be identifiedb. protein received its name from a childhood tumor of the retinac. protein and cyclin-dependent kinase inhibitors put brakes on cells’ S-phase

entryd. all of these are true*

[22] Total cell output from mitotic divisions of the cortical progenitors can be stated as

a. the P (progenitor) fractionb. the Q (quit) fractionc. the P (progenitor) plus Q (quit) fractions*d. the P (progenitor) minus Q (quit) fractions

[23] Knockout mice in which p27-kip has been genetically deleteda. have a lower Q fraction and thus a thicker cerebral cortex*b. have a lower Q fraction and thus a thinner cerebral cortexc. have a higher Q fraction and thus a thicker cerebral cortexd. have no changes in the Q-P ratio

[24] Signals that stimulate proliferation of all mitotic cells are called ________factors and are named for the tissues or cell types where they have ________ effects.

a. Growth mitogenic*b. Transcription signalingc. Secretion inhibitoryd. Secretion stimulatory

[25] The receptors for various mitogenic factors that are expressed on progenitor cells variably respond to different mitogens depending upon

a. The location of the progenitor cellb. The stage of development of the progenitor cellc. Both the location and stage of development of the progenitor cell*d. Neither the location nor the stage of development of the progenitor cell

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[26] Calegari has recently proposed that, as the cell cycle gets progressively longer, this directly causes the progenitors to switch to generating additional progenitors, thus prolonging the P fraction and shortening the Q fraction.

a. Trueb. False*

[27] The ratio of cell types produced by many multipotent progenitors is variable and thus the lineages are considered indeterminate.

a. True*b. False

[28] Epidermal growth factor (EGF), ciliary neuronotrphic factor (CNTF) and bone morphogenic proteins (BMPs) are likely to cause progenitor cells to develop into

a. Astrocytes*b. Oligodendrocytesc. Neuronsd. Macroglia

[29] If the Notch receptor is blocked, genetically or with the application of specific inhibitors, progenitor cells will prematurely differentiate into

a. Astrocytesb. Oligodendrocytesc. Neurons*d. Macroglia

[30] What do proneural bHLH genes do?

a. Block the differentiation of progenitor cells into astrocytes*b. Block the differentiation of progenitor cells into neuronsc. Block mitosis to maintain progenitor cells as progenitorsd. Signal interkinetic nuclear migration

[31] If one of the daughter cells from mitotic division of a progenitor cell expresses a higher level of neurogenin than its sister, it will also express more Dll, which by a feedback loop activates ________ in the progenitor’s sister cell, lowering its level of Dll, leaving that cell with more _________ free to differentiate as a neuron.

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a. Notch neurogenin*b. Hes1 notchc. Neurogenin Notchd. Hes1 neurogenin

[32] The more direct role of Notch in gliogenesis occurs because

a. Notch induces demethylation of the STAT3 binding site of the GFAP promoter, and, induces expression of a glial promoting transcription factor, NFIA*

b. Notch induces methylation of the DNA in the promoters of glial-specific genes thus inhibiting acess of STAT3

c. Notch induces the expression of BMP and CNTF, to promote gliogenesisd. Suppressing or deactivating Notch induces the expression of NFIA, a glial

promoting transcription factor

[33] Glial promoting transcription factor NFIA can also repress neurogenesis in progenitor cells.

a. True*b. False

[34] Two transcription factors Olig1 and Olig2 are specifically expressed in the __________ zone; the over-expression of either Olig1 or Olig2 can induce additional ___________.

a. pMN oligodendrocytes*b. ventral ventricular glial cellsc. dorsal ectodermal oligodendrocytesd. pMN motor neurons

[35] Progenitor cells whose initial fate is a motor neuron and whose ultimate fate is an oligodendrocyte, go through a cycle of expressing the proneural gene ________ which combined with Olig1/2 produce motor neurons; later, this gene is turned off, leading to production of the transcription factor ___________ which combine with Olig1/2 to create oligodendrocytes.

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a. neurog2 Nkx2.2*b. Hes5 GFAPc. Neurog2 NeuroD1d. Nkx2.2 Hes5

[36] The process by which architecturally organized brain regions can be understood in terms of the timing of neurogenesis is called histogenesis.

a. True*b. False

[37] The ratio of increase in size of the surface area of the cerebral cortex from mouse to human being is

a. Tenfoldb. Hundredfoldc. Thousandfold*d. Ten thousandfold

[38] The dramatic increase in size of the cerebral cortex in human beings has been accompanied by an increase in specialization; it is estimated that there are at least _______ different regions that can be identified on the basis of their cytoarchitecture, differences in the relative numbers of neurons in each of the cortex’s six layers.

a. 55b. 50*c. 45d. 40

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[39] Following the development of progenitor cells in the ventricular zone, the stages of histogenesis of the cerebral cortex, in temporal order, are

a. (1) Formation of apical progenitors (Radial glia) and intermediate precursor cells (2) division of preplate into Cajal-Retzius cells and subplate cells and (3) Migration of neurons along radial glial fibers to form the cortical plate*

b. (1) division of preplate into Cajal-Retzius cells and subplate cells (2) Migration of neurons along radial glial fibers to form the cortical plate and (3) Formation of apical progenitors (Radial glia) and intermediate precursor cells

c. (1) Migration of neurons along radial glial fibers to form the cortical plate (2) division of preplate into Cajal-Retzius cells and subplate cells and (3) Formation of apical progenitors (Radial glia) and intermediate precursor cells

d. (1) Formation of apical progenitors (Radial glia) and intermediate precursor cells (2) Migration of neurons along radial glial fibers to form the cortical plate and (3) division of preplate into Cajal-Retzius cells and subplate cells

[40] The Intermediate Progenitor Cell model for how the different cortical regions develop (e.g. motor cortex has more neurons in one layer, sensory cortex has more neurons in another layer) proposes

a. Changes in the number of mitotic divisions of IPCs at different developmental times, thus changing the number of neurons in inner layer V earlier than outer layer IV*

b. IPCs migrate from the ventricular zone to different cortical layers in proportion to the eventual number of neurons in each layer, more to layer IV for sensory and more to layer V for motor cortex

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c. Changes in the number of mitotic divisions of IPCs at different developmental times, thus changing the number of neurons in outer layer V earlier than inner layer IV

d. IPCs migrate from the ventricular zone to different cortical layers in proportion to the eventual number of neurons in each layer, more to layer IV for motor and more to layer V for sensory cortex

[41] Ventricular zone apical progenitor cells

a. Give rise to most of the neurons in the cerebral cortexb. give rise to “radial glial processes” that extend from the ventricular to the

pial surfacec. provide a scaffolding which migrating neurons cling to as they move to their

final destinationd. all of these are true*

[42] In regionally distinct regions of cortex the number of cortical columns created by apical progenitor cells and their progeny varies across mammals, reaching a maximum number in most regions of human cerebral cortex.

a. True*b. False

[43] Some neurons in the cerebral cortex migrate tangentially rather than radially; these neurons

a. Use GABA as their neurotransmitter rather than glutamate*b. Use glutamate as their neurotransmitter rather than GABAc. Are produced from progenitors found in a particular region of the ventricular

zoned. Derive from specialized IPCs in radial columns from which they migrate to

adjacent radial columns

[44] The most numerous type of neuron in the brain is the

a. Cerebellar granule cell*b. Motor neuronc. Sensory neuron

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d. Astrocyte and oligodendrocyte

[45] Neurons of the cerebellum, Purkinje, stellate, basket and granule cells, are all generated from a ventricular zone near the fourth ventricle, in a manner analogous to neurons of the cerebral cortex.

a. Trueb. False*

[46] What is the ‘external granule layer’?

a. A secondary zone of neurogenesis*b. Final location of cerebellar granule cellsc. A zone near the hippocampus where progenitors of hippocampal granule

cells migrate to before continuing neurogenesisd. All of these are correct

[47] What are Bergman glia?

a. A type of radial glial cell that guides Purkinje cells to their final location in the Purkinje layer of the cerebellar cortex

b. A type of radial glial cell that guides granule cells to their final location in the granule layer of the cerebellar cortex*

c. A type of radial glial cell that guides migrating neurons to their final location in different layers of the cerebral cortex

d. All of these are correct

[48] In the cerebellum, Purkinje cells produce the mitogen Shh and granule cell progenitors express Shh receptors, patched and smoothened, a mechanism that controls the number of

a. Purkinje cellsb. Granule cells*c. Bergman glial cellsd. Both Purkinje and granule cells

[49] Children with mutations in the Shh receptor patched

a. Will develop a Medulloblastoma*

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b. Will have an over-production of Purkinje cellsc. Will have too few granule cellsd. All of these are true

[50] The naturally-occuring mutant mouse strain called _________ has been particularly informative in studies of neuronal migration.

a. Reeler*b. Staggererc. Weaverd. All of these are true

[51] Studies of the large glycoprotein Reelin have identified additional components to its complex signal transduction pathway controlling neuronal migration and include

a. Dab1, VLDLR and ApoER2*b. VLDLR, ApoER2 and Shhc. Patched, smoothened and Shhd. Reelin, weaving and staggerin

[52] The current model of how reelin works suggests that

a. It acts as an attractant to bring migrating cells to the Cajal-Retzius cell layerb. It acts as a stop signal at the cortical surface, telling cells to stop moving in

that direction and form a new cortical layerc. It acts as both a stop signal and as a go signal, first activating then degrading

Dab1*d. Merely the presence of reelin is necessary and sufficient for correct neuronal

migration

[53] Other molecules found to be critical for correct neuroblast migration, to establish the normal layered architecture of the cerebral cortex are integrins

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(adhesion molecules) and neuregulins (glial growth factors). Among the roles of these molecules are

a. Enabling migrating neurons to attach to glia b. Enabling the formation of the pia extracellular marix*c. Controlling the formation of the correct number of radial gliald. All of these are correct

[54] Post-embryonic development of the frog eye

a. Only changes size; no new neural cells are addedb. Grows by adding new neural cells in the center, pushing out the normal-

functioning peripheral cellsc. Grows by adding new neural cells in the periphery, adding to the normal-

functioning central cells*d. Continues until the frog has to use its visual system to catch prey, and then

post-embryonic development ceases

[55] In the frog and the fish, the ciliary marginal zone (CMZ)

a. Contains retinal stem cells capable of generating all different types of retinal neurons*

b. Primarily contains progenitors for retinal ganglion cells, which are also being added by progenitors in the optic tectum

c. Contains an unlayered (no gradient) mix of progenitors; as these differentiate into retinal ganglion cells they migrate to the edge closest to the mature retina

d. None of these are correct

[56] Adult, post-embryonic neurogenesis only occurs in the mammalian hippocampus.

a. Trueb. False*

[57] In most species of animals some new neurons are generated post-embryonically.

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a. True*b. False

[58] Seasonally-regulated changes in the number of neurons in songbirds” HVC nucleus appears to be regulated by

a. Seasonal change in levels of testosterone control the number of neuronsb. Neurons generated in the spring have a longer average lifespan than those

generated in the fallc. Neurons generated in the fall have a longer average lifespan than those

generated in the spring*d. Neurons migrating from the ventricular zone have a longer lifespan than

those generated in the HVC itself

[59] Regarding neurogenesis in the post-embryonic rodent brain

a. It occurs in many brain areas right after birthb. May be identified by H-thymidine birthdating up to 4 weeks postnatallyc. Neurons continue to migrate from the subventricular zone to the olfactory

bulb for up to a month post-natallyd. All of these are correct*

[60] Migrating neurons in the RMS (rostral migrating stream) of the rodent, connecting the subventricular zone (SVZ) to the olfactory bulb,

a. Chain-migrate along elongated glial cells much like migrating neurons in the cerebellum

b. Wrap around radial glial cells much like migrating neurons in the cortexc. Form a somewhat unique structure of chains by attaching to each other*

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d. All of these are correct

[61] Retroviral labeling (GFP) of mitotically active cells in the adult rat demonstrated that the dentate gyrus of the hippocampus

a. Exhibits neurogenesis only for several months after birthb. Exhibits neurogenesis for the entire lifespan; microelectrode recording

indicates poor integration of these granule cells into hippocampal functionc. Exhibits neurogenesis for the entire lifespan; microelectrode recording

indicates good integration of these granule cells into hippocampal function*d. None of these are correct

[62] A beta-galactosidase labeled study of neurons in mouse olfactory bulb and hippocampus demonstrated that [[only 14% of]] hippocampal granule cells were newly generated in the adult mouse.

a. A small percentage, 14%*b. A majority, 65%c. Almost all, 99%d. no

[63] Altman’s evolutionary thesis –stability and rigidity along with plasticity and flexibility-- is that the second stage of neurogenesis, when the larger or macroneurons are generated later in development, is a mechanism for environmental influences to regulate neurogenesis, making the brain more fit for its environment.

a. Trueb. False*

[64] The EMT of neural crest cells is similar to the first steps of

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a. Metastasis in invasive cancers*b. Migratory neurons leaving the ventricular zone and moving to their

designated laminar level in the cerebral cortexc. Migration of GABA containing stellate cells arising from the lateral

ganglionic eminenced. The short radial migration of Purkinje cells from the ventricular zone near

the fourth ventricle

[65] Key processes in the epithelial to mesenchymal transition (EMT) of premigratory neural crest cells involve losing the apical tight junctions to each other:

a. The protein Occludin is downregulated; the transcription factors twist, slug and snail downregulate N-Cadherin and Occludin; then the cells secrete matrix metalloproteases (MMPs) that digest the extracellular matrix of the basal lamina*

b. The protein Occludin is upregulated; the transcription factors twist, slug and snail upregulate N-Cadherin and Occludin; then the cells secrete matrix metalloproteases (MMPs) that digest the extracellular matrix of the basal lamina

c. The protein Occludin is downregulated; the transcription factors twist, slug and snail upregulate N-Cadherin and Occludin; then the cells secrete matrix metalloproteases (MMPs) that digest the extracellular matrix of the basal lamina

d. The protein Occludin is upregulated; the transcription factors twist, slug and snail downregulate N-Cadherin and Occludin; then the cells secrete matrix metalloproteases (MMPs) that digest the extracellular matrix of the basal lamina

[66] The migration of early neural crest cells is supported by their expression of receptors for

a. Integrin proteins*

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b. glutamatec. Occludin proteinsd. Neural Cadherin

[67] Neural crest cells migrate in interspersed streams along channeled migratory routes; many of the guidance molecules (factors) such as semaphorins, EphrinB or EphB are

a. Inhibitory or repulsive*b. Excitatory or attractivec. Repulsive or attractive at different times according to what molecules or

their receptors are being expressedd. Use physical guidance, like the radial glial processes

[68] Neural crest cells display contact inhibition of locomotion which is a. Homotypic*b. Heterotypicc. can be either homotypic or heterotypic depending on where the cells happen

to be at the timed. all of these are correct

[69] The lack of heterotypic contact inhibition

a. keeps migrating cells away from cells of different typesb. allows migrating cells to invade the space of cells of different types*

[70] Transplantation of neural crest cells from anterior (enteric ganglion forming) levels of the embryo to more posterior regions results in

a. the anterior crest cells following the posterior pathways and making sympathetic neurons*

b. the anterior crest cells following anterior pathways and making sympathetic neurons

c. the anterior crest cells following the posterior pathways and making enteric ganglion neurons

d. the anterior crest cells following anterior pathways and making enteric ganglion neurons

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