The loss of scents: Do defects in olfactory sensory neuron development underlie human disease?

Abstract

The olfactory system is a fascinating and beguiling sensory system: olfactory sensory neurons detect odors underlying behaviors essential for mate choice, food selection, and escape from predators, among others. These sensory neurons are unique in that they have dendrites contacting the outside world, yet their first synapse lies in the central nervous system. The information entering the central nervous system is used to create odor memories that play a profound role in recognition of individuals, places, and appropriate foods. Here, the structure of the olfactory epithelium is given as an overview to discuss the origin of the olfactory placode, the plasticity of the olfactory sensory neurons, and finally the origins of the gonadotropin-releasing hormone neuroendocrine cells. For the purposes of this review, the development of the peripheral sensory system will be analyzed, incorporating recently published studies highlighting the potential novelties in development mechanisms. Specifically, an emerging model where the olfactory epithelium and olfactory bulb develop simultaneously from a continuous neurectoderm patterned at the end of gastrulation, and the multiple origins of the gonadotropin-releasing hormone neuroendocrine cells associated with the olfactory sensory system development will be presented. Advances in the understanding of the basic mechanisms underlying olfactory sensory system development allows for a more thorough understanding of the potential causes of human disease.

Dissecting the neural divide: a continuous neurectoderm gives rise to the olfactory placode and bulb

“…Thus our results support a role for Dlx3b/4b in regulating a balance between OE and OB precursors at the progenitor levels ensuring the proper segregation cells during olfactory field separation. Taken together, our data suggest that the olfactory system develops as a functional unit, where the peripheral sensory epithelium (the source) and the OB (the central target) develop in tandem, instead of as separate pieces that integrate once formed (Whitlock, 2008(Whitlock, , 2015.…”

Association of olfactory neuropathy spectrum disorder and Wolff‐Parkinson‐White syndrome: A Report of a case

“…MRI can be helpful in the workup of cases of anosmia or hyposmia (congenital or new-onset), as MRI can evaluate the presence of the olfactory nerves Kallmann syndrome is the most common syndrome associated with congenital anosmia. 5,6 Kallmann syndrome is a rare disease and there is a high degree of genetic variation, and only approximately 40% of Kallmann syndrome is caused by known genetic mutations. A thorough description of the known mutations involved in Kallmann syndrome is beyond the scope of this case report, but has been well summarized and includes many gene loci, including the X-linked KAL1 (ANOS1) (accounting for approximately 10%-20% of Kallmann syndrome patients), FGFR1, FGF8, and many others.…”

“…A thorough description of the known mutations involved in Kallmann syndrome is beyond the scope of this case report, but has been well summarized and includes many gene loci, including the X-linked KAL1 (ANOS1) (accounting for approximately 10%-20% of Kallmann syndrome patients), FGFR1, FGF8, and many others. 5,6 The nasal placode is a source of forebrain GnRH cells, and the involvement of the GnRH pathway in both the reproductive and olfactory systems is thought to account for the common hypogonadotropic hypogonadism and anosmia seen in Kallmann syndrome. The olfactory placodes form in the ventrorostral area of the developing vertebrate brain and form from neural crest cells and non-neural ectoderm.…”

“…[1][2][3][4] Kallmann syndrome is a disorder characterized by hypogonadotropic hypogonadism and congenital absence of the olfactory bulbs and is likely the most well-known cause of congenital anosmia. 5,6 In this syndrome, patients present with lack of sexual development and delayed or absent puberty, as well as anosmia. Female patients may not undergo puberty until placed on exogenous hormones, for example, oral contraceptives.…”

“…While postinfectious, age‐related, post‐traumatic, or disease‐related (eg, diabetes, Parkinson's disease) hyposmia or anosmia is relatively common and well described, congenital hyposmia or anosmia is quite rare 1‐4 . Kallmann syndrome is a disorder characterized by hypogonadotropic hypogonadism and congenital absence of the olfactory bulbs and is likely the most well‐known cause of congenital anosmia 5,6 . In this syndrome, patients present with lack of sexual development and delayed or absent puberty, as well as anosmia.…”