The contribution of robos to olfactory sensory axon targeting in the olfactory bulb Jessica Brandt Herr

Format:

Book

Thesis/Dissertation

Author/Creator:

Herr, Jessica Brandt, author.

Contributor:

University of Pennsylvania. Cell and Molecular Biology., degree granting institution.

Language:

English

Subjects (All):

Neurosciences.

Biology.

Genetics.

0317.

0306.

0369.

Local Subjects:

Neurosciences.

Biology.

Genetics.

0317.

0306.

0369.

Genre:

Academic theses

Physical Description:

1 online resource (104 pages)

Contained In:

Dissertations Abstracts International 87-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2026

Language Note:

English

Summary:

The zebrafish olfactory system provides a powerful model for studying early neural circuit development due to its remarkable simplicity and unparalleled access to the early stages of development. Each Olfactory Sensory Neuron (OSN) expresses a single Odorant Receptor (OR) and projects an axon from the olfactory epithelium to individually identifiable neuropil structures in the olfactory bulb known as protoglomeruli. OSNs expressing ORs from homology Clade A or B project to the Central Zone (CZ) protoglomerulus, and those expressing ORs from homology Clade C project to the Dorsal Zone (DZ) protoglomerulus. Single cell RNA-sequencing has identified robo2 as being more highly expressed in Clade C-expressing OSNs than Clade A- and Clade B-expressing OSNs. Zebrafish, mouse, and Drosophila each require Slit-Robo signaling for proper targeting of OSN axons, yet it remains unclear whether each Robo receptor and Slit ligand serve specialized or redundant functions in the developing olfactory bulb. A CRISPR-based F0 approach was utilized to examine the contributions Robo axonal guidance receptors make to OSN axon targeting of protoglomeruli. Loss of robo2 results in misprojection of both CZ- and DZ-projecting OSN axons. Robo2 is expressed at higher levels in DZ-projecting OSNs and concordant with this, DZ-projecting axons misproject more frequently than CZ-projecting axons upon loss of robo2. In the absence of robo2, robo1 contributes to DZ-targeting, but not to CZ-targeting. Thus, there is an OSN subtype-dependent contribution of Robo receptors to vertebrate olfactory circuit assembly. Loss of robo1 or robo3 by themselves has no observable effect on OSN axon guidance. Loss of any single Slit paralog and simultaneous loss of two Slit paralogs results in no observable OSN axon guidance defects. These results suggest that all slits function redundantly, so that the loss of any single slit gene is compensated for by the remaining paralogs. Both slit1a and netrin1b are expressed near the olfactory epithelium exit in the developing zebrafish olfactory system. In the absence of Slit-Robo signaling, we propose Netrin1b diverts axons at the exit point to ectopic midline locations. I propose that a balance between Slit-Robo repulsion and counteracting attractive signals promote accurate OSN axon targeting

Notes:

Source: Dissertations Abstracts International, Volume: 87-12, Section: B.

Advisors: Raper, Jonathan A. Committee members: Granato, Michael; Bashaw, Greg J.; Ma, Minghong; Klein, Peter

Ph.D. University of Pennsylvania 2026

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798247982197

Access Restriction:

Restricted for use by site license