2012 Group Project 3
Introduction to the Gustatory System
Timeline of Developmental Processes of the Gustatory System
- Sensory Taste Development; UNSW Embryology
- Embryonic and early fetal development of human taste buds: a transmission electron microscopical study  - Can't access full article!
- Scanning electron microscopical studies of developing gustatory papillae in humans. 
- Innervation of developing human taste buds. An immunohistochemical study 
- Evidence for stimulus access to taste cells and nerves during development: an electron microscopic study. 
|Week 6||* The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <refname=PMID9455607><pubmed>9455607</pubmed></ref>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum  . On the dorsal midline the first circumvallate papilla develops (Figure 2) |
|Weeks 6 to 7||Nerve fibres approach the basal lamina of lingual epithelium . At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation.|
|Week 7||* A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) .|
|Week 8||* The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina  and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week . However, at this time these cells are still poorly differentiated, elongated epithelial cells  . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system . Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear .|
|Weeks 8-9||“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) |
|Weeks 10-11||* At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed .
* Fungiform papillae appear on the lateral margins and the tip of the tongue , containing taste bud primordial that display the first signs of a primitive pore formation . * Untypically differentiated apical cellular processes extend onto the surface  * Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4)  
|Week 12||Taste bud cells are more clearly differentiated into epithelial cell types II and III .|
|Weeks 12-13||By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) . There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure .|
|Weeks 14 -15||The shape of the taste buds primordial begins to resemble those of adult taste buds . By the 14th week the taste pores develop as the taste pits are filled by microvilli , indicating the possibility that the taste buds begin their gustatory function , however they still lack an electron-dense mucous material (Fig.10) . The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit .|
History of Discoveries
|350BC||Aristotle writes about the basic tastes, sweet and bitter, which can be modified, he says, by salty and acidic.|
|1901||D. Hanig publishes a paper containing data of taste sensitivity in different regions of the tongue. The data are later misinterpreted, giving rise to the myth of the ‘tongue map’|
|1908||Fifth basic taste discovered: savouriness, described as umami, which is conferred by glutamate.|
|1931||Bitter taste sensitivity found to vary among humans (1)|
|1931-32||Genetecists confirm findings about sensitivity to bitter tasting PTC and discover non-tasting is a recessive genetic trait (2,11)|
|1939||Geneticists show that chimpansees like humans, vary in their ability to perceive the bitterness of PTC|
|1992||Discovery of gustucin, a teste cell-specific G-protein, in the taste buds. Gustucin is later shown to mark bitter, umami and sweet cells (13)|
|2000||First taste sonsors, the T2R receptors, discovered (3)|
|2001||The sweet receptor is discovered (5): a combination of TaR2 and T1R3.|
|2002||Amino acid detector, T1R1 and T1R3 identified (6) = Umami|
|2005||Sweet taste receptor found (15) in the GI tract|
|2006||Cells for sour taste discovered, identified by PKD2L1 (4-7)|
|2009||The Car4 receptor, which senses the carbon dioxide in fizzy drinks is found on sour cells (8)|
|2010||ENaC identified as the sodium-salt taste receptor (9)|
Adult Tongue and Taste Buds – Structure and Function
The tongue is for tasting, swallowing, and speech.The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number. The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing. The larger, less numerous fungiform papillae are scattered among the filiform papillae where as the Circumvallate papilae form a wide V at the sulcus terminalis. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.
The Image Below is a very simplistic Hand drawn Diagram of the surface of the Tongue showing the locations of the different papillae & and also the sulcus terminalis, This image indicates the tongue from an above veiw
The functional unit of the taste bud is a taste cells, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded. The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.
The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale
(try to include technologies to detect abnormalities during pregnancy)
Knocking out P2X Receptors
Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.
In Huang, 2008 [PMID:21940456] this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).
When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.
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FGF signalling and genes
Sprouty, or Srpy, genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.
By knocking out Spry genes using mice which had Spry1 and Spry2 knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between Spry1/2 and Fgf10 is that Spry1/2 antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of Fgf10 in the mesenchyme is necessary for the formation of CVP.
"'Insert figure 1 from article"'
Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).
Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived fromt he ectoderm and the posterior tongue is derived from the endoderm ??? check article (& why is it necessary to know why different areas of the tongue are derived from different areas
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development. The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.
the below image shows histological stains of a mice tongue
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities  Another Animal Study involving mice explores a new idea of Neural crest contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. Appreciating embryonic courses allows constant monitoring throughout expansion of the foetus. In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium.  Research by Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function.  Brain-derived neurotrophic factor (BDNF) was identified to promote gustatory neuron development, along with identifying the embryonic precursor populations for cranial ganglia in mice through the use of fate mapping in a study by Harlow, Yang, Williams, Barlow (2011) The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. 
The below image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement 
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