Bcl11b controls odorant receptor class choice in mice.

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Olfactory sensory neurons (OSNs) in mice express a single odorant receptor (OR) gene from either class I or class II repertoires.
• The regulatory mechanisms governing this crucial OR class choice in OSNs are not yet understood.

Purpose of the Study:

• To elucidate the molecular mechanisms controlling odorant receptor (OR) class choice in olfactory sensory neurons (OSNs).
• To identify key transcription factors involved in determining whether an OSN expresses a class I or class II OR gene.

Main Methods:

• Utilized loss- and gain-of-function analyses of the transcription factor Bcl11b in mouse olfactory sensory neurons (OSNs).
• Performed OSN-specific genetic manipulations to alter Bcl11b expression levels.
• Assessed the impact of these manipulations on OR class choice and olfactory behaviors.

Main Results:

• Demonstrated that the transcription factor Bcl11b is a critical determinant of OR class choice in OSNs.
• Showed that class I is the default OSN fate, and Bcl11b enforces class II OR expression by inhibiting a class I enhancer (J-element).
• Generated mice with biased OR class expression ('class I-dominant' and 'class II-dominant') exhibiting distinct innate olfactory behaviors.

Conclusions:

• Identified a novel transcriptional mechanism, centered on Bcl11b, that mediates a binary switch for OR class selection in the olfactory system.
• This mechanism is essential for the proper anatomical and functional organization of the mammalian olfactory system.
• Bcl11b's role in OR class choice highlights its importance in olfactory perception and behavior.