Molecular Mechanisms in Mouse Olfactory System

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Questions and Answers

What is the main function of odorant receptors (ORs) in the mouse olfactory system?

  • To transmit signals to the brain via the olfactory bulb
  • To regulate the expression of other genes
  • To control the growth and development of olfactory sensory neurons
  • To detect and bind to specific odorants (correct)

How many different types of odorant receptors are estimated to be expressed in the mouse olfactory system?

  • 500
  • 10,000
  • 1000 (correct)
  • 100

What is the unique feature of olfactory sensory neuron (OSN) expression of odorant receptors?

  • OR expression changes over time in each OSN
  • Each OSN expresses multiple ORs
  • OSNs express only one functional OR gene in a monoallelic manner (correct)
  • OR expression is random in each OSN

What is the role of cyclic adenosine monophosphate (cAMP) in olfactory sensory neuron (OSN) axonal projection?

<p>cAMP signals are used by ORs to instruct anterior-posterior (A-P) axonal projection (D)</p> Signup and view all the answers

What is the difference between the dorsal-ventral (D-V) and anterior-posterior (A-P) axonal projection of olfactory sensory neurons (OSNs)?

<p>D-V projection is regulated by anatomical location of OSNs, while A-P projection is instructed by OR expression and cAMP signaling (C)</p> Signup and view all the answers

What happens to the olfactory map after birth?

<p>The map is further refined in an activity-dependent manner (C)</p> Signup and view all the answers

What is the role of glomerular structures in the olfactory map?

<p>Glomeruli are the sites of synapse formation between OSN axons and olfactory bulb neurons (A)</p> Signup and view all the answers

What is the primary focus of the research summarized in this article?

<p>The developmental processes of the olfactory map formation in the mouse (A)</p> Signup and view all the answers

What is the role of the enzyme/selector in the activation of OR genes?

<p>It removes methylations from H3K9me3 and H4K20me3 at a stochastically chosen locus activating its transcription. (D)</p> Signup and view all the answers

What is the primary mechanism by which ORs regulate axon guidance and sorting?

<p>Generating cAMP signals that influence transcription of relevant molecules. (C)</p> Signup and view all the answers

Which of the following molecules is involved in the down-regulation of LSD1 after a functional OR gene is activated?

<p>ACIII (D)</p> Signup and view all the answers

What is the term used to describe the phenomenon where an olfactory sensory neuron (OSN) expresses only one functional olfactory receptor (OR) gene?

<p>One neuron-one receptor rule (D)</p> Signup and view all the answers

What is the proposed function of the H region in regulating OR gene choice?

<p>It modifies the chromatin structure, influencing the accessibility of OR promoters. (C)</p> Signup and view all the answers

What is the primary function of the unfolded protein response in the context of OR gene expression?

<p>To suppress further activation of OR genes. (A)</p> Signup and view all the answers

Which of the following is NOT a method used to detect OR molecules in the olfactory system?

<p>In situ hybridization. (A)</p> Signup and view all the answers

How does the activity-dependent regulation of glomerular segregation molecules differ from the regulation of A-P targeting molecules?

<p>Glomerular segregation molecules are regulated in an activity-dependent manner, while A-P targeting molecules are not. (C)</p> Signup and view all the answers

What is the significance of the enrichment of H3K4me3 in an activated OR-gene region?

<p>It signals the activation of the OR gene. (C)</p> Signup and view all the answers

Based on the knockout studies of the H region, what can be concluded about its mode of action?

<p>H acts only in <em>cis</em> to regulate OR gene choice. (C)</p> Signup and view all the answers

What is the primary function of OR-instructed axonal projection in the olfactory system?

<p>To guide the OSN to its specific glomerulus in the olfactory bulb. (A)</p> Signup and view all the answers

Why was it initially thought that OR proteins might function as guidance or adhesion molecules?

<p>They were reported to exhibit homophilic interactions. (D)</p> Signup and view all the answers

What is the significance of the unique expression area of each OR gene in the olfactory epithelium (OE)?

<p>It ensures that specific ORs are expressed in specific regions of the OE. (C)</p> Signup and view all the answers

What is the primary function of cAMP in the context of OR gene expression?

<p>To regulate the transcription of axon guidance and sorting molecules. (B)</p> Signup and view all the answers

Which of these is NOT mentioned as a potential mechanism for regulating OR gene choice?

<p>Competition between different OR genes for binding to the H region. (C)</p> Signup and view all the answers

Which of these is NOT a key factor implicated in the singular OR expression in each OSN?

<p>Activity-dependent regulation of glomerular segregation molecules. (B)</p> Signup and view all the answers

Why were the theories of irreversible DNA changes and gene conversion dismissed as explanations for single OR gene expression?

<p>Because they were not supported by experimental evidence. (A)</p> Signup and view all the answers

What is the 'one neuron-one receptor rule' referring to?

<p>Each neuron in the olfactory system expresses only one type of olfactory receptor gene. (A)</p> Signup and view all the answers

What is the role of the LCR in the regulation of OR gene expression?

<p>The LCR acts as a platform where multiple transcription factors can bind to regulate OR gene expression. (D)</p> Signup and view all the answers

According to the content, what is the possible role of Msx1 and Foxg1 in regulating OR gene choice?

<p>They are both transcription factors that can directly activate the expression of particular OR genes. (A)</p> Signup and view all the answers

How does the expression of a functional OR gene affect the expression of other OR genes in the same neuron?

<p>The functional OR gene product acts as a negative feedback regulator, inhibiting the activation of other OR genes. (C)</p> Signup and view all the answers

According to the content, what is the primary mechanism that ensures single OR gene expression in a neuron?

<p>The stochastic nature of LCR-promoter interactions coupled with negative feedback regulation by the functional OR gene product. (B)</p> Signup and view all the answers

Which of the following best explains why the olfactory system can detect a vast array of odors despite the 'one neuron-one receptor rule'?

<p>The olfactory system employs a diverse population of neurons, each expressing a different OR gene, collectively enabling the detection of a vast array of odors. (A)</p> Signup and view all the answers

What is the key difference between the theories of irreversible DNA changes and gene conversion and the LCR-promoter interaction model?

<p>Irreversible DNA changes and gene conversion rely on permanent changes to the DNA sequence, while the LCR-promoter interaction model involves transient interactions. (C)</p> Signup and view all the answers

What is the primary function of Golf?

<p>Regulating glomerular segregation. (D)</p> Signup and view all the answers

What percentage of amino acid identity do Gs and Golf share?

<p>88% (C)</p> Signup and view all the answers

Which of the following is NOT a characteristic of the A-P targeting pathway?

<p>It regulates the expression of glomerular segregation molecules. (B)</p> Signup and view all the answers

How does the level of cAMP influence the A-P targeting process?

<p>It activates PKA, which phosphorylates transcription factors involved in A-P targeting. (A)</p> Signup and view all the answers

What is the primary function of Gs in the context of odorant receptor signaling?

<p>Generating a unique level of cAMP based on agonist-independent activity. (D)</p> Signup and view all the answers

How does a conditional knockout of Gs affect the expression of A-P targeting molecules?

<p>It decreases the expression levels. (D)</p> Signup and view all the answers

Which of the following is true regarding the relationship between glomerular segregation and A-P targeting?

<p>A-P targeting is independent of glomerular segregation. (B)</p> Signup and view all the answers

What is the primary role of Kirrel2 and Kirrel3 in the olfactory system?

<p>Mediating the signaling pathway for glomerular separation. (A)</p> Signup and view all the answers

What are the two distinct processes involved in the formation of a neural map in the mouse olfactory system?

<p>OR-dependent (A-P targeting) and OR-independent (D-V targeting) (C)</p> Signup and view all the answers

What is the major difference in the source of cAMP signals that leads to the observed distribution of A-P targeting and glomerular segregation molecules?

<p>A-P targeting relies on constitutive OR signaling, while glomerular segregation relies on stimulus-driven neuronal activity. (C)</p> Signup and view all the answers

During which developmental stage does the refinement of the neural map occur in an activity-dependent manner?

<p>Neonatal period (D)</p> Signup and view all the answers

What is the role of Golf in the olfactory system?

<p>Golf plays a role in glomerular segregation in mature OSNs. (D)</p> Signup and view all the answers

How does the equilibrium of conformational transition of GPCRs influence the expression of A-P targeting molecules?

<p>It influences the steady-state levels of cAMP in immature OSNs. (D)</p> Signup and view all the answers

What is the role of neuronal activity in the expression of glomerular segregation molecules?

<p>It is regulated by stimulus-driven neuronal activity. (C)</p> Signup and view all the answers

Which of the following describes the major basis for the observed difference in the distribution of A-P targeting (graded) and glomerular segregation (mosaic) molecules?

<p>The difference in the source of cAMP signals. (B)</p> Signup and view all the answers

What is the main conclusion of the study regarding the regulation of A-P targeting and glomerular segregation?

<p>A-P targeting is regulated by the steady-state levels of cAMP, while glomerular segregation is regulated by neuronal activity. (C)</p> Signup and view all the answers

Flashcards

Olfactory Sensory Neurons (OSNs)

Neurons that detect odorants using specialized receptors.

Odorant Receptors (ORs)

Approximately 1000 different receptors that bind to specific odorant molecules.

Monogenic Expression

Each OSN expresses only one functional OR gene.

Neural Map

Spatial representation of sensory information in the brain.

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Anterior-Posterior (A-P) Projection

OSNs extend axons based on OR expression along the front-back axis.

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Dorsal-Ventral (D-V) Projection

Axonal projection regulated by anatomical structures along the top-bottom axis.

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Glomeruli

Structures in the olfactory bulb where OSNs with the same OR converge.

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Cyclic Adenosine Monophosphate (cAMP)

A signaling molecule involved in OR-dependent A-P projections.

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OR gene expression

Activation of a single olfactory receptor gene in neurons.

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Stochastic choice

Random selection process for gene activation.

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LCR

Locus Control Region that influences gene expression.

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Negative feedback

Regulatory mechanism to inhibit further gene activation.

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One neuron-one receptor rule

Each olfactory neuron expresses only one type of receptor.

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Cell lineage

The ancestry of cells that can influence gene choice.

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Transcription factors

Proteins that bind to DNA to regulate gene expression.

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Zone-specific factors

Transcription factors that are restricted to certain cell zones.

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OR-gene locus

A specific region in the genome where olfactory receptor (OR) genes are located and regulated.

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H3K4me3

A histone modification associated with active gene transcription, marking the OR-gene region when silenced.

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LSD1

A histone demethylase that plays a role in the activation and suppression of OR genes in olfactory sensory neurons.

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cAMP

Cyclic adenosine monophosphate, a secondary messenger involved in transmitting signals from OR activation to neuronal activity.

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Adenylyl cyclase type III (ACIII)

An enzyme activated by the olfactory-specific G protein (Golf) that converts ATP to cAMP in OSNs.

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Mouse olfactory system

The sensory system in mice responsible for detecting odors and processing olfactory signals.

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Glomerular secretion molecules

Molecules that are regulated in an activity-dependent manner with a mosaic distribution in glomerular maps.

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Homophilic interaction

A process where similar axons, guided by OR proteins, recognize and interact with each other.

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A-P targeting molecules

Molecules involved in anterior-posterior targeting, distinct from glomerular segregation molecules.

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Negative feedback signals

Signals that prevent the activation of additional OR-gene loci once one functional gene is expressed.

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OR gene choice

The process where each olfactory sensory neuron (OSN) selects one functional olfactory receptor (OR) gene to express.

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Cis vs Trans regulation

Cis regulation acts on the same DNA molecule, while trans regulation involves different molecules interacting.

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cAMP as second messenger

A signaling molecule that transmits signals within cells, involved in the regulation of OR expression.

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Trans-acting enhancer

A regulatory element that enables the activation of a gene from a different location on the genome.

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H region

A genetic area proposed to regulate the expression of olfactory receptor genes, acting in cis.

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Gs Protein

A G-protein that mediates odorant receptor signals and shares similarity with Golf.

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Golf Protein

A G-protein involved in olfactory signal transduction, structurally similar to Gs.

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A-P Targeting

The mechanism that uses OR activity to regulate molecules like Nrp1 and PlxnA1.

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Neuronal Activity

Electrical activities of mature OSNs that influence glomerular segregation and target molecule levels.

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PKA

Protein Kinase A that activates transcription factors like CREB through phosphorylation.

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CREB

A transcription factor activated by PKA that plays a role in A-P targeting and glomerular segregation.

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Glomerular Segregation

The process regulated by neuronal activity that determines the distribution of OSNs in the olfactory bulb.

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Olfactory Signal Regulation

The process by which OR signals regulate A-P targeting in OSNs.

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Cilia Localization in OSNs

In mature OSNs, ORs are primarily located in the cilia.

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Axon Termini Role

In immature OSNs, ORs are found at the axon termini, influencing development.

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Temporal and Spatial Insulation

Differential regulation of OR signals based on timing and location.

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Conformational Transition of GPCRs

The change in GPCR shape that affects cAMP levels in OSNs.

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Graded A-P Targeting

A-P targeting whose strength varies based on cAMP signals in OSNs.

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Mosaic Glomerular Map

The unique distribution pattern of glomeruli formed by different OSNs.

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Stimulus-Driven Regulation

Regulation of glomerular segregation molecules influenced by neuron activity.

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Study Notes

Mouse Olfactory System Neural Map Formation

  • Odorants detected by ~1000 different odorant receptors (ORs) in olfactory sensory neurons (OSNs)
  • Each OSN expresses only one functional OR gene
  • OSN axons expressing the same OR converge on glomeruli in the olfactory bulb (OB)
  • Early development forms a coarse map via two processes:
    • OR-independent axonal projection along the dorsal-ventral (D-V) axis, determined by anatomical OSN location in the olfactory epithelium (OE)
    • OR-dependent projection along the anterior-posterior (A-P) axis, guided by OR molecules and cyclic AMP (cAMP) signals
  • Postnatal, map refinement converts continuous map to discrete through glomerular structure segregation, activity-dependent process
  • OR gene expression regulated by stochastic activation by cis-acting LCRs (locus control regions)
  • H and P regions identified; the H region's 124-bp core-H region sufficient for enhancer activity
  • Homeodomain factors Lhx2 and Emx2 bind OR promoter regions, potentially remodeling chromatin structure for OR activation
  • Single OR gene activation by cis-acting LCR potentially stochastic
  • OR expression restricted by OSN location
  • Negative feedback regulation by expressed OR molecules prevents further activation of other OR genes

OR Gene Choice

  • Single neuron-one receptor rule in the mouse olfactory system ensures expression of only one functional OR gene in each OSN
  • This gene choice mechanism crucial for axonal projection of OSNs to OB
  • Theories like DNA recombination and gene conversion discarded
  • Potential for a locus control region (LCR) regulating single OR gene choice, in cis

OR-Instructed OSN Projection

  • OR molecules are detected on axon termini; thought to recognize target cues in OB
  • ORs regulate transcription levels of axon guidance and sorting molecules via cAMP.
  • This contrasts with visual system where relative positional information in the periphery is preserved during projection to the brain
  • cAMP generation crucial; OR-derived cAMP signals guide A-P targeting
  • OR-independent D-V projection determined by anatomical OE OSN location, regulated by repulsive ligands and receptors (Slits/Robo2 and Sema3F/Nrp2)

A-P Targeting of OSN Axons

  • cAMP signals drive A-P targeting
  • High cAMP levels for posterior projection, low levels for anterior projection.
  • Neuropilin 1 (Nrp1) expression levels in axon termini establish anterior-posterior gradient in OB
  • Developmentally regulated; mature OSNs process odor-related activities to refine structure

Temporal Regulation of D-V targeting

  • Differentiated maturation of OSNs along D-V axis, with earlier maturation in the dorsal region and later maturation in the ventral region.
  • Sema3F produced by earlier maturing OSNs in the anterodorsal region of OB; repels Sema3F-negative OSNs and drives D-V targeting in the OB.
  • Robo2 and Slit1 interactions are also believed to play a part in the development of the olfactory map.

Activity-Dependent Map Refinement

  • The final stages of the map involves activity-dependent glomerular segregation, which occur postnatally and continue refining the continuous map to a discrete map
  • Activity-dependent segregation process involves interaction between neighboring axons, either through adhesive or repulsive interactions of molecules like Kirrel2, Kirrel3 and ephrin-A and EphA
  • Mosaic distribution and expression of these molecules are regulated through OR activity; important for refining the map.

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Developmental Regulation of Neural Map Formation in the Mouse Olfactory System PDF

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