Talk:Sensory - Smell Development

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Cite this page: Hill, M.A. (2021, October 17) Embryology Sensory - Smell Development. Retrieved from


The perceptual logic of smell

Curr Opin Neurobiol. 2014 Jan 14;25C:107-115. doi: 10.1016/j.conb.2013.12.010. [Epub ahead of print]

Secundo L1, Snitz K1, Sobel N2. Author information


Mammals have ∼1000 different olfactory receptor subtypes, each responding to a number of different odorants, and each odorant activating a number of different receptor subtypes. These molecular and anatomical underpinnings of olfaction imply a perceptual structure of very high dimensionality that relies on combinatorial coding. In contrast to this expectation, the study of olfactory perception reveals a structure of much lower dimensionality. Moreover, a low-dimensionality approach to olfaction enabled derivation of perception-based structural metrics for smell. These metrics provided meaningful predictions of odorant-induced neural activity and perception from odorant structure alone. Based on this low functional dimensionality, we speculate that olfaction likely does not functionally rely on 1000 different receptor subtypes, and their persistence in evolution may imply that they have additional roles in non-olfactory functions such as in guidance of embryogenesis and development. Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID 24440370


Non-redundant coding of aversive odours in the main olfactory pathway

Nature. 2013 May 23;497(7450):486-9. doi: 10.1038/nature12114. Epub 2013 Apr 28.

Dewan A1, Pacifico R, Zhan R, Rinberg D, Bozza T. Author information


Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor. The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception. Comment in Sensory systems: Encoding aversion. [Nat Rev Neurosci. 2013]

PMID 23624375


Close association of olfactory placode precursors and cranial neural crest cells does not predestine cell mixing

Delopmental Dynamics

Maegan V. Harden1, Luisa Pereiro2, Mirana Ramialison3,†, Jochen Wittbrodt3, Megana K. Prasad4, Andrew S. McCallion4, Kathleen E. Whitlock2,‡,*

Vertebrate sensory organs originate from both cranial neural crest cells (CNCCs) and placodes. Previously we have shown that the olfactory placode (OP) forms from a large field of cells extending caudally to the pre-migratory neural crest domain, and that OPs form through cell movements and not cell division. Concurrent with OP formation CNCCs migrate rostrally to populate the frontal mass. However, little is known about the interactions between CNCCs and the placodes that form the olfactory sensory system. Previous reports suggest that the OP can generate cell types more typical of neural crest lineages such as neuroendocrine cells and glia, thus marking the OP as an unusual sensory placode. One possible explanation for this exception is that the neural crest origin of glia and neurons has been overlooked due to the intimate associated of these two fields during migration. Using molecular markers and live imaging, we followed the development of OP precursors and of dorsally migrating CNCCs in zebrafish embryos. We generated a six4b:mCherry line (OP precursors) that, with a sox10:EGFP line (CNCCs), was used to follow cell migration. Our analyses showed that CNCCs associate with and eventually surround the forming OP with limited cell mixing occurring during this process.;jsessionid=0CBAF650CB4A7BDEB726B708B4AA45EB.d04t01


The dual origin of the peripheral olfactory system: placode and neural crest

Mol Brain. 2011 Sep 23;4:34. Katoh H, Shibata S, Fukuda K, Sato M, Satoh E, Nagoshi N, Minematsu T, Matsuzaki Y, Akazawa C, Toyama Y, Nakamura M, Okano H. Source Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. Abstract BACKGROUND: The olfactory epithelium (OE) has a unique capacity for continuous neurogenesis, extending axons to the olfactory bulb with the assistance of olfactory ensheathing cells (OECs). The OE and OECs have been believed to develop solely from the olfactory placode, while the neural crest (NC) cells have been believed to contribute only the underlying structural elements of the olfactory system. In order to further elucidate the role of NC cells in olfactory development, we examined the olfactory system in the transgenic mice Wnt1-Cre/Floxed-EGFP and P0-Cre/Floxed-EGFP, in which migrating NC cells and its descendents permanently express GFP, and conducted transposon-mediated cell lineage tracing studies in chick embryos. RESULTS: Examination of these transgenic mice revealed GFP-positive cells in the OE, demonstrating that NC-derived cells give rise to OE cells with morphologic and antigenic properties identical to placode-derived cells. OECs were also positive for GFP, confirming their NC origin. Cell lineage tracing studies performed in chick embryos confirmed the migration of NC cells into the OE. Furthermore, spheres cultured from the dissociated cells of the olfactory mucosa demonstrated self-renewal and trilineage differentiation capacities (neurons, glial cells, and myofibroblasts), demonstrating the presence of NC progenitors in the olfactory mucosa. CONCLUSION: Our data demonstrates that the NC plays a larger role in the development of the olfactory system than previously believed, and suggests that NC-derived cells may in part be responsible for the remarkable capacity of the OE for neurogenesis and regeneration.

PMID 21943152

Loss-of-function mutations in sodium channel Nav1.7 cause anosmia

Nature. 2011 Apr 14;472(7342):186-90. Epub 2011 Mar 23.

Weiss J, Pyrski M, Jacobi E, Bufe B, Willnecker V, Schick B, Zizzari P, Gossage SJ, Greer CA, Leinders-Zufall T, Woods CG, Wood JN, Zufall F. Source Department of Physiology, University of Saarland School of Medicine, 66421 Homburg, Germany.

Abstract Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell. Comment in Nature. 2011 Apr 14;472(7342):173-4.

PMID 21441906


The cell biology of smell

J Cell Biol. 2010 Nov 1;191(3):443-52.

DeMaria S, Ngai J.

Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA. Abstract The olfactory system detects and discriminates myriad chemical structures across a wide range of concentrations. To meet this task, the system utilizes a large family of G protein-coupled receptors-the odorant receptors-which are the chemical sensors underlying the perception of smell. Interestingly, the odorant receptors are also involved in a number of developmental decisions, including the regulation of their own expression and the patterning of the olfactory sensory neurons' synaptic connections in the brain. This review will focus on the diverse roles of the odorant receptor in the function and development of the olfactory system.

PMID: 21041441

Anosmia Predicts Hypogonadotropic Hypogonadism in CHARGE Syndrome

Bergman JE, Bocca G, Hoefsloot LH, Meiners LC, van Ravenswaaij-Arts CM. J Pediatr. 2010 Sep 29.

OBJECTIVE: To test the hypothesis that a smell test could predict the occurrence of hypogonadotropic hypogonadism (HH) in patients with CHARGE syndrome, which is a variable combination of ocular coloboma, heart defects, choanal atresia, retardation of growth/development, genital hypoplasia, and ear anomalies or hearing loss caused by mutations in the CHD7 (chromodomain helicase DNA binding protein 7) gene.

STUDY DESIGN: We performed endocrine studies and smell testing (University of Pennsylvania Smell Identification Test) in 35 adolescent patients with molecularly confirmed CHARGE syndrome.

RESULTS: Complete data on smell and puberty were available for 15 patients; 11 patients had both anosmia and HH, whereas 4 patients had normosmia/hyposmia and spontaneous puberty. In addition, 7 boys were highly suspected of having HH (they were too young for definite HH diagnosis, but all had cryptorchidism, micropenis, or both) and had anosmia. The type of CHD7 mutation could not predict HH because a father and daughter with the same CHD7 mutation were discordant for HH and anosmia.

CONCLUSION: Anosmia and HH were highly correlated in our cohort, and therefore smell testing seems to be an attractive method for predicting the occurrence of HH in patients with CHARGE syndrome. The use of this test could prevent delay of hormonal pubertal induction, resulting in an age-appropriate puberty.

PMID: 20884005


Development of olfactory and related structures in staged human embryos

Anat Embryol (Berl). 1980;161(2):225-36.

Bossy J.


The staged sequence of development of the olfactory and related structures has been established from the serially sectioned human embryos of the Carnegie collection, from stage 11 to stage 23. The nasal epiblastic thickening appears at stage 11 and the nasal field is well outlined at stage 12. At stage 15, a continuous cellulovascular strand is observed between the nasal groove and the olfactory field. The vomeronasal groove appears at stage 16 (O'Rahilly 1967). During stage 17, the olfactory nerve is organized into two plexuses, lateral and medial, the latter mingled with the terminal-vomeronasal complex. The olfactory bulb begins to appear at stage 18. Stage 19 is characterized by the individualization of the olfactory bulb and nuclei. In addition, the distinction between olfactory structures and terminal and vomeronasal ones begins to be clear. The structure of the olfactory bulb is evident at stage 21. At stage 23, the olfactory strands are well individualized, and olfactory and terminal-vomeronasal fibers are easily distinguishable. The terminal ganglion is rather terminal-vomeronasal with an autonomic terminal contingent and a sensory one attached to the vomeronasal system.

PMID 7469043