# Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function

## TL;DR

This study explores how Prok2 gene mutations disrupt olfactory development and function, leading to defects in the olfactory system seen in Kallmann syndrome.

## Contribution

The study identifies downstream genes of Prok2 that mediate olfactory system organization during development.

## Key findings

- Prok2 knockout mice show diminished olfactory signal detection and disrupted maturation of olfactory sensory neurons.
- Downstream genes of Prok2, including intermediate filament genes, are critical for olfactory system development.
- Defective Prok2 signaling leads to abnormal olfactory bulb layer development and impaired olfactory function.

## Abstract

Olfaction is important for the quality of life; however, in Kallmann syndrome (KS), defective development results in olfactory dysfunction. Notably, the mechanism underlying olfactory development, especially in the olfactory epithelium (OE), which detects olfactory signals, remains unclear. Mutations in PROK2, which encodes prokineticin-2, have been identified in approximately 9% of the KS patients with olfactory defects.

We examined olfactory function and analyzed the causes of olfactory dysfunction based on spatiotemporal development and gene expression changes in Prok2 knockout (KO) model mice with KS.

The ability of the OE to detect olfactory signals was diminished in adult Prok2 KO mice. Maturation of olfactory sensory neurons (OSNs) in the OE and formation of glomeruli in the olfactory bulb (OB) in adult Prok2 KO mice were disrupted, thus causing olfactory dysfunction. Furthermore, molecular analysis of Prok2 KO mice during embryonic development revealed abnormal development of OB layers and diminished differentiation to mature OSNs in the OE at the later stage, which caused defects in the entire olfactory system. Remarkably, downstream signaling genes of Prok2, including intermediate filament genes and genes expressed in the putative OB, were found to mediate olfactory system organization.

Overall, these findings reveal the role of Prok2 in olfactory system organization and elucidate how olfactory development defects translate to olfactory function.