Many animals use the sense of smell as a guide through life, dividing the world into what is good and what is harmful. Olfaction distinguishes nutritional foods from toxic ones, helps identify appropriate mates, and allows the detection of predators. A lot of effort has gone into elucidating how odours are detected and how they are met with the appropriate behavioural response, processes that are still incompletely understood.

However, evidence is now emerging that, in addition to its roles in acutely sensing odours, olfaction is involved in the regulation of the general physiology of animals. In the roundworm Caenorhabditis elegans and the fruit fly Drosophila melanogaster the olfactory system regulates life span, as animals that have compromised olfaction live longer than their ‘smelling’ counterparts. This exciting discovery left many scientists scratching their heads: how on earth could olfaction have such a dramatic effect on physiology?

A chance discovery in a study by a team of researchers led by Utpal Banerjee at the University of California, Los Angeles, USA, recently published in the journal Cell, provides a possible answer. This research group focuses on the process of haematopoiesis – blood cell development – in the Drosophila larva, trying to elucidate the mechanisms that tightly regulate the generation of differentiated blood cells from a group of stem cell-like progenitors. They noticed that when they interfered with a receptor for the neurotransmitter GABA within blood cell progenitors, most of them differentiated precociously into blood cells. This suggests the nervous system is involved in the regulation of the generation of blood cells. To find out more about how this neurotransmitter regulates haematopoiesis, they set out to pinpoint its exact source.

They found a cluster of cells in the brain that secrete GABA into the larval blood to be responsible, as blocking the production of neurotransmitter within these cells led to precocious differentiation of progenitors into blood cells. This demonstrates the nervous system is indeed directly involved in haematopoiesis, but what could be the function of this regulation?

In order to address this question, the team tried to find the parts of the nervous system that induce the secretory cells to release GABA. They made the key discovery that inhibition of the olfactory system prevents the release of neurotransmitter from the secretory cells.

This inhibition subsequently leads to the precocious differentiation of progenitor cells, suggesting that the detection of smells is required for the maintenance of the pre-differentiated state of blood progenitor cells.

What makes this finding particularly interesting is that it provides a possible mechanism for how olfaction affects life span: in the absence of odours, or if the olfactory system is inhibited, the number of blood cells that is being generated is increased. As these cells are involved in many aspects of innate immunity, this increase in number could leave the organism better protected against microbial agents and help the animal to live longer.

The findings suggest that olfaction directly regulates haematopoiesis, whereby the activation of an odorant receptor is required for the maintenance of the pre-differentiated state of the pool of cells that give rise to blood cells. While the evidence presented provides a strong link between olfaction and the regulation of blood cells, and the link to life span extension is an attractive one, don't start blocking up your nose just yet: it is not yet known whether similar mechanisms are present in vertebrates (such as yourself).

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Olfactory control of blood progenitor maintenance