These notes introduce the abnormal development of the sense of smell or olfaction: nasal placode, olfactory epithelium, olfactory bulb, vomeronasal organ.
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Stage 13 |
Stage 22 |
Early embryonic: nasal placode |
Late embryonic: nasal conchae |
Recent research has shown a relationship between what the receptive epithelium is exposed too and how the central neural pathway develops, similar to that shown earlier for the visual system.
Anosmia is the term used to describe having no sense of smell. Anosmia/hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts.
Page Links: Introduction | Some Recent Findings | Anosmia | Kallmann Syndrome | Reading | Development Overview | Olfactory Pathway | Vomeronasal | Developmental Genes |References | Glossary
The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. Hardelin JP, Dodé C. Sex Dev. 2008;2(4-5):181-93.
"Kallmann syndrome (KS) combines hypogonadotropic hypogonadism and anosmia. Anosmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to gonadotropin-releasing hormone (GnRH) deficiency, which presumably results from a failure of the embryonic migration of neuroendocrine GnRH cells from the olfactory epithelium to the forebrain."
The term used to describe having no sense of smell. Anosmia/hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts.
A developmental disease affecting both the hormonal reproductive axis and the sense of smell. Affected individuals have mutations in either of two different genes KAL1 and FGFR1 (20%) and prokineticin receptor-2 (PROKR2) or prokineticin-2 (PROK2) genes (10%).
X-linked form of Kallmann syndrome (KAL1) encodes a protein, anosmin, that plays a key role in the migration of GnRH neurons and olfactory nerves to the hypothalamus.
(OMIM - KAL1)
Autosomal Kallmann syndrome (KAL2) is caused by mutation in the gene encoding fibroblast growth factor receptor-1.
(OMIM - KAL2)
Kallmann syndrome (KAL3) is caused by mutation in the PROKR2 gene
Kallmann syndrome (KAL4) is caused by mutation in the PROK2 gene
Kallmann syndrome (KAL5) is caused by mutation in the CHD7 gene.
Developmental Biology (6th ed.) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. The Kallman Syndrome: Sex, Smell, and Specific Adhesion
Molecular Biology of the Cell (4th ed.) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. Smell and Vision Depend on G-Protein-linked Receptors That Regulate Cyclic-Nucleotide-gated Ion Channels | The Formation of an Entire Organ Can Be Triggered by a Single Gene Regulatory Protein | Sensory Epithelia
Neuroscience (2nd ed.) Purves, Dale; Augustine, George.J.; Fitzpatrick, David; Katz, Lawrence.C.; LaMantia, Anthony-Samuel.; McNamara, James.O.; Williams, S. Mark, editors. Sunderland (MA): Sinauer Associates, Inc. 2001 Olfactory Perception in Humans |
Odours bind to and activate olfactory receptors located on the dendrites of sensory neurons in the nose and how the mitral cells of the olfactory bulb (OB) process olfactory information. What has yet to be thoroughly described is how the piriform cortex receives and transforms information arriving from the OB via the lateral olfactory tract (LOT). Although the cell types present in the piriform cortex are known (Shepherd, 2004), previous work has failed to differentiate between disparate electrophysiological profiles and synaptic contacts made between principal cells.
Olfactory receptor neurons (ORNs) - odours bind and activate olfactory receptors located on dendrites of sensory neurons in the nose.
Olfactory bulb (OB) - Mitral cells process olfactory information (encoded in a chemotopic map).
Lateral olfactory tract (LOT) - pathway to cortex.
Primary olfactory cortex (= Piriform cortex) - receives and transforms information.
The vomeronasal accessory olfactory system is involved in detecting and transfering pheromone information to the neuroendocrine hypothalamus. (More? Witt M, Hummel T., 2006 | Puberty)
Olfactory Placode
radial glia-like progenitor (RGLP) express nestin
↓
Foxg1?
↓
proliferating cells express Ascl1 (Mash1)
↓
Ngn1 and NeuroD immediate neuronal precursors
Ascl1 - (Mash1) bHLH transcription factor
BIG-2/contactin-4 - axonal glycoprotein (immunoglobulin superfamily) expressed in a subpopulation of mouse olfactory sensory neurons.
Foxg1 - winged helix transcription factor, expressed in an early progenitor population of the olfactory placode.
insulin-like growth factor - (IGF) signaling is required for sensory innervation of the lateral olfactory bulb.
Retinoic acid - Rawson NE, LaMantia AS. Once and again: retinoic acid signaling in the developing and regenerating olfactory pathway. J Neurobiol. 2006 Jun;66(7):653-76.
Robos - (Robo1, Robo2) Slit receptor protein
Slit - (Slit1, Slit2) axon guidance molecule
Dlx3, Dlx5, Pax6
Reviews
Wilson RI, Mainen ZF. Early events in olfactory processing. Annu Rev Neurosci. 2006;29:163-201.
Rawson NE, LaMantia AS. Once and again: retinoic acid signaling in the developing and regenerating olfactory pathway. J Neurobiol. 2006 Jun;66(7):653-76.
Witt M, Hummel T. Vomeronasal versus olfactory epithelium: is there a cellular basis for human vomeronasal perception? Int Rev Cytol. 2006;248:209-59.
Stockhorst U, Pietrowsky R. Olfactory perception, communication, and the nose-to-brain pathway. Physiol Behav. 2004 Oct 30;83(1):3-11.
Calof AL. Sex, nose and genotype. Curr Biol. 1992 Feb;2(2):103-5.
Articles
Scolnick JA, Cui K, Duggan CD, Xuan S, Yuan XB, Efstratiadis A, Ngai J. Role of IGF signaling in olfactory sensory map formation and axon guidance. Neuron. 2008 Mar 27;57(6):847-57.
Kaneko-Goto T, Yoshihara S, Miyazaki H, Yoshihara Y. BIG-2 mediates olfactory axon convergence to target glomeruli. Neuron. 2008 Mar 27;57(6):834-46.
Bras-Pereira C, Bessa J, Casares F. Odd-skipped genes specify the signaling center that triggers retinogenesis in Drosophila. Development. 2006 Oct 4
Evans AL, Gage PJ. Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development. Hum Mol Genet. 2005 Nov 15;14(22):3347-59.
Delaunay-El Allam M, Marlier L, Schaal B. Learning at the breast: preference formation for an artificial scent and its attraction against the odor of maternal milk. Infant Behav Dev. 2006 Jul;29(3):308-21.
Schaal B, Marlier L, Soussignan R. Human foetuses learn odours from their pregnant mother's diet. Chem Senses. 2000 Dec;25(6):729-37.
Soussignan R, Schaal B, Marlier L. Olfactory alliesthesia in human neonates: prandial state and stimulus familiarity modulate facial and autonomic responses to milk odors. Dev Psychobiol. 1999 Jul;35(1):3-14.
Schaal B, Marlier L, Soussignan R. Olfactory function in the human fetus: evidence from selective neonatal responsiveness to the odor of amniotic fluid. Behav Neurosci. 1998 Dec;112(6):1438-49.
Marlier L, Schaal B, Soussignan R. Neonatal responsiveness to the odor of amniotic and lacteal fluids: a test of perinatal chemosensory continuity. Child Dev. 1998 Jun;69(3):611-23.
Search PubMed: Feb 2007 "olfactory development" 3,773 reference articles of which 338 were reviews.
Search PubMed Now: olfactory development | smell development | vomeronasal development
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These notes introduce the development of the sense of smell or olfaction.
Note the different spellings "odour" (UK) or "odor" (USA).
A French research group has recently been investigating the development of smell in the fetus and in neonates.
The nasal epithelium has also been a researh "hot topic" as it is one of the few easily accessible sites of adult neural stem cells. (More? Stem Cells)
If you have not studied the development of smell an overview of developmental timing and a text overview.
Please email Dr Mark Hill if you wish to make a comment about this current project.