Sniffing out olfactory neurogenesis

By Sriivatsan G Rajan and Ankur Saxena

What is this?

A high magnification video of a zebrafish embryo demonstrates sensory neurogenesis in the developing nose (olfactory epithelium), with newly forming neurons labeled in orange and blue cells indicating high Notch signaling activity. The developing eye is also visible nearby. The olfactory epithelium houses remarkable levels of neuroregeneration, including in humans, and is a robust model for investigating the molecular pathways that drive continuous neuronal renewal.

Where can this be found?

Zebrafish are ray-finned fish that are native to freshwater habitats in South Asia and are widely used as vertebrate model systems due to their high degree of genetic similarity to humans. We use a suite of tools to genetically manipulate the organisms, and the optically transparent embryos are amenable to high-resolution microscopy.

How was this taken?

We performed live confocal microscopy of transgenic zebrafish embryos at 2 days post-fertilization (dpf). The embryos expressed red fluorescent protein (orange) in olfactory sensory neurons and destabilized green fluorescent protein (blue) in cells with active Notch signaling. Images were acquired at regularly spaced time intervals for 15 hours using a Zeiss LSM 800 confocal microscope and stitched together to make this timelapse video.

What happens during olfactory sensory neuron (OSN) development?

We discovered that during olfactory sensory neuron (OSN) development, discrete groups of progenitor/stem cells communicate with each other via a unique Notch/Insm1a signaling module to form neighborhoods of cells that act as hot spots of neurogenesis (generation of new neurons). Retinoic acid signaling from the nearby eye influences this intricate process of new OSN formation, and BDNF (brain-derived neurotrophic factor) signaling helps guide new neurons to their final destinations.  

Why should people care about this?

Neurodegenerative disorders are strongly associated with the depletion of neurons across the nervous system. Interestingly, while olfactory sensory neurons (OSNs) are known to be highly regenerative, the loss of smell is often an early indicator of potential neurodegeneration. As a first step to understanding this apparent paradox, we aimed to uncover how new OSNs are generated. Additionally, we hope to discover conserved pathways that might aid neuroregeneration in other organ systems. Finally, our observations of the close coordination and exchange of signals between the nose and the eye shed light on the importance of inter-organ communication for neurogenesis.  

How would you explain this to an 8-year-old?

Our noses have tiny nerve cells that detect different kinds of smells that help you enjoy pizza or not enjoy medicine. While zebrafish don’t eat pizza (as far as we know), they have those types of cells, too. Because you can see through zebrafish pretty well, we can put them under a fancy microscope, watch those nerve cells get made, and learn how that happens. What we learn then allows us to think of ways to make new nerve cells that could help people and keep them healthy.

Where can people find out more about it?

You can read our recent paper in Stem Cell Reports https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(25)00179-1; read a short news story about it https://www.uab.edu/news/research-innovation/sniffing-out-how-neurons-are-made; and check out the fun journal cover image https://www.cell.com/stem-cell-reports/issue?pii=S2213-6711(24)X0010-7#fullCover

(No Ratings Yet)

Loading...