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?

cAMP signals are used by ORs to instruct anterior-posterior (A-P) axonal projection (D) 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)?

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

What happens to the olfactory map after birth?

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

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

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

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

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

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

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

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

Generating cAMP signals that influence transcription of relevant molecules. (C) 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?

ACIII (D) 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?

One neuron-one receptor rule (D) Signup and view all the answers

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

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

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

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

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

In situ hybridization. (A) 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?

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Activity-dependent regulation of glomerular segregation molecules. (B) 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?

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

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

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

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

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

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

They are both transcription factors that can directly activate the expression of particular OR genes. (A) 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?

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

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

The stochastic nature of LCR-promoter interactions coupled with negative feedback regulation by the functional OR gene product. (B) 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'?

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) 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?

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

What is the primary function of Golf?

Regulating glomerular segregation. (D) Signup and view all the answers

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

88% (C) Signup and view all the answers

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

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

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

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

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

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

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

It decreases the expression levels. (D) Signup and view all the answers

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

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

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

Mediating the signaling pathway for glomerular separation. (A) 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?

OR-dependent (A-P targeting) and OR-independent (D-V targeting) (C) 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?

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

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

Neonatal period (D) Signup and view all the answers

What is the role of Golf in the olfactory system?

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

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

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

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

It is regulated by stimulus-driven neuronal activity. (C) 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?

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

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

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

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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Description

Explore the intricate workings of the mouse olfactory system with this quiz. Delve into the functions of odorant receptors, their expression in olfactory sensory neurons, and the role of various molecular mechanisms. Test your knowledge on axonal projections, glomerular structures, and the unique processes that shape olfactory maps.