Tongue Development

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Introduction

Fetal tongue (week 12)
Fetal tongue (week 12)

The tongue's embryonic orgin is derived from all pharyngeal arches contributing different components. As the tongue (Latin, lingua; Greek, glossa) develops "inside" the floor of the oral cavity, it is not readily visible in the external views of the embryonic (Carnegie) stages of development. Tongue muscle cells originate from somites mesoderm, while muscles of mastication derive from the unsegmented somitomeres. This current page gives a brief overview of early tongue development.


The dorsal tongue is covered by a stratified squamous epithelium, with numerous papillae and taste buds. There are also 8 to 12 circumvallate papillae arranged in an inverted V-shape towards the base of the tongue. These notes cover development of the muscular tongue, not the sense of taste.

Taste Links: Introduction | Student project | Tongue Development | Category:Taste
Historic Taste 
Historic Embryology: 1888 human infant papilla foliata | 1889 man taste-organs | Paper - Further observations on the development of the taste-organs of man|1889 further man taste-organs]]


gastrointestinal tract | head | Category:Tongue

Historic Embryology - Tongue
1902 Tongue | 1917 von Ebner's glands | 1921 Tongue

Some Recent Findings

Tongue position in the oral cavity.
  • Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature[1] "The tongue is a highly specialised muscular organ with a complex anatomy required for normal function. We have utilised multiple genetic approaches to investigate local temporospatial requirements for sonic hedgehog (SHH) signalling during tongue development. Mice lacking a Shh cis-enhancer, MFCS4 (ShhMFCS4/-), with reduced SHH in dorsal tongue epithelium have perturbed lingual septum tendon formation and disrupted intrinsic muscle patterning, with these defects reproduced following global Shh deletion from E10.5 in pCag-CreERTM; Shhflox/flox embryos. SHH responsiveness was diminished in local cranial neural crest cell (CNCC) populations in both mutants, with SHH targeting these cells through the primary cilium. CNCC-specific deletion of orofaciodigital syndrome 1 (Ofd1), which encodes a ciliary protein, in Wnt1-Cre; Ofdfl/Y mice led to a complete loss of normal myotube arrangement and hypoglossia. In contrast, mesoderm-specific deletion of Ofd1 in Mesp1-Cre; Ofdfl/Y embryos resulted in normal intrinsic muscle arrangement. Collectively, these findings suggest key temporospatial requirements for local SHH signalling in tongue development (specifically, lingual tendon differentiation and intrinsic muscle patterning through signalling to CNCCs) and provide further mechanistic insight into the tongue anomalies seen in patients with disrupted hedgehog signalling."
  • SOX2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis[2] "Adult tongue epithelium is continuously renewed from epithelial progenitor cells, a process that requires hedgehog (HH) signaling. In mice, pharmacological inhibition of the HH pathway causes taste bud loss within a few weeks. Previously, we demonstrated that sonic hedgehog (SHH) over-expression in lingual progenitors induces ectopic taste buds with locally increased SOX2 expression, suggesting that taste bud differentiation depends on SOX2 downstream of HH. To test this, we inhibited HH signaling in mice and observed a rapid decline in Sox2 and SOX2-GFP expression in taste epithelium. Upon conditional deletion of Sox2, differentiation of both taste and non-taste epithelial cells was blocked, and progenitor cell number increased. In contrast to basally restricted proliferation in controls, dividing cells were overabundant and spread to supra-basal epithelial layers in mutants. SOX2 loss in progenitors also led non-cell-autonomously to taste cell apoptosis, dramatically shortening taste cell lifespans. Finally, in tongues with conditional Sox2 deletion and SHH over-expression, ectopic and endogenous taste buds were not detectable; instead, progenitor hyperproliferation expanded throughout the lingual epithelium. In summary, we show that SOX2 functions downstream of HH signaling to regulate lingual epithelium homeostasis." SOX
  • Review - How to make a tongue: Cellular and molecular regulation of muscle and connective tissue formation during mammalian tongue development[3] The vertebrate tongue is a complex muscular organ situated in the oral cavity and involved in multiple functions including mastication, taste sensation, articulation and the maintenance of oral health. Although the gross embryological contributions to tongue formation have been known for many years, it is only relatively recently that the molecular pathways regulating these processes have begun to be discovered. In particular, there is now evidence that the Hedgehog, TGF-beta, WNT and Notch signaling pathways all play an important role in mediating appropriate signaling interactions between the epithelial, cranial neural crest and mesodermal cell populations that are required to form the tongue. In humans, a number of congenital abnormalities that affect gross morphology of the tongue have also been described, occurring in isolation or as part of a developmental syndrome, which can greatly impact on the health and well-being of affected individuals. These anomalies can range from an absence of tongue formation (aglossia) through to diminutive (microglossia), enlarged (macroglossia) or bifid tongue."
  • A Wnt/Notch/PAX7 signaling network supports tissue integrity in tongue development[4] "The tongue is one of the major structures involved in human food intake and speech. Tongue malformations such as aglossia, microglossia, and ankyloglossia are congenital birth defects, greatly affecting individuals' quality of life. However, the molecular basis of the tissue-tissue interactions that ensure tissue morphogenesis to form a functional tongue remains largely unknown. Here we show that ShhCre -mediated epithelial deletion of Wntless (Wls), the key regulator for intracellular Wnt trafficking, leads to lingual hypoplasia in mice. Disruption of epithelial Wnt production by Wls deletion in epithelial cells led to a failure in lingual epidermal stratification and loss of the lamina propria and the underlying superior longitudinal muscle in developing mouse tongues. These defective phenotypes resulted from a reduction in epithelial basal cells positive for the basal epidermal marker protein p63 and from impaired proliferation and differentiation in connective tissue and paired box 3 (Pax3)- and Pax7-positive muscle progenitor cells. We also found that epithelial WNT production is required for activation of the Notch signaling pathway, which promotes proliferation of myogenic progenitor cells. Notch signaling in turn negatively regulated Wnt signaling during tongue morphogenesis. We further show that Pax7 is a direct Notch target gene in the embryonic tongue."
More recent papers  
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More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Tongue Development | Tongue Embryology

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Noncanonical transforming growth factor β (TGF-beta) signaling in cranial neural crest cells causes tongue muscle developmental defects[5] "Microglossia is a congenital birth defect in humans and adversely impacts quality of life. In vertebrates, tongue muscle derives from the cranial mesoderm, whereas tendons and connective tissues in the craniofacial region originate from cranial neural crest (CNC) cells....Thus, our data indicate that CNC-derived fibroblasts regulate the fate of mesoderm-derived myoblasts through TGFβ-mediated regulation of FGF and BMP signaling during tongue development."
  • Mice with TGFβ activated kinase 1 (Tak1) deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development[6] "The repressive effect of the Tak1-mediated noncanonical TGFβ signaling on Fgf10 expression was further confirmed by inhibition of p38, a downstream kinase of Tak1, in the primary cell culture of developing tongue. Tak1 thus functions to regulate tongue development by controlling Fgf10 expression and could represent a candidate gene for mutation in human PRS clefting." FGF
  • Bone morphogenetic protein-2 (BMP2)functions as a negative regulator in the differentiation of myoblasts, but not as an inducer for the formations of cartilage and bone in mouse embryonic tongue[7] "In vitro studies using the myogenic cell line C2C12 demonstrate that bone morphogenetic protein-2 (BMP-2) converts the developmental pathway of C2C12 from a myogenic cell lineage to an osteoblastic cell lineage. Further, in vivo studies using null mutation mice demonstrate that BMPs inhibit the specification of the developmental fate of myogenic progenitor cells. ...BMP-2 functions as a negative regulator for the final differentiation of tongue myoblasts, but not as an inducer for the formation of cartilage and bone in cultured tongue, probably because the genes related to myogenesis are in an activation mode, while the genes related to chondrogenesis and osteogenesis are in a silencing mode."
  • Shh and ROCK1 modulate the dynamic epithelial morphogenesis in circumvallate papilla development[8] "In rodents, a circumvallate papilla (CVP) develops with dynamic changes in epithelial morphogenesis during early tongue development. Molecular and cellular studies of CVP development revealed that there would be two different mechanisms in the apex and the trench wall forming regions with specific expression patterns of Wnt11 and Shh. ...Wnt, a well known key molecule to initiate taste papillae, would govern Rho activation and cytoskeleton formation in the apex epithelium of CVP. In contrast, Shh regulates the cell proliferation to differentiate taste buds and to invaginate the epithelium for development of von Ebner's gland (VEG)."

Pharyngeal Arch Contributions

The tongue has contributions from all pharyngeal arches which changes with time. The tongue initially begins as swelling rostral to foramen cecum, the median tongue bud.

Animation shows the sequence of development of the tongue. The different colours represents the relative contribution from each pharyngeal arch.

  • Arch 1 - oral part of tongue (anterior 3/2)
  • Arch 2 - initial contribution to surface is lost
  • Arch 3 - pharyngeal part of tongue (posterior 1/3)
  • Arch 4 - epiglottis and adjacent regions
Tongue.gif
Tongue 001 icon.jpg
 ‎‎Tongue
Page | Play

Embryonic

Human embryonic tongue 01.jpg

Human embryonic tongue development (mid-sagittal section)[9]

Week 4

Stage13 sem3.jpg Gray0979.jpg


Links: Carnegie stage 13 | Week 4

Week 8

These histology images are from the Carnegie Stage 22 human embryo.

Stage 22 image 060.jpg Stage 22 image 061.jpg
Stage 22 image 062.jpg Stage 22 image 063.jpg

Carnegie Stage 23 oral cavity floor

Carnegie Stage 23 oral cavity floor
Stage23 embryo oral cavity 01.jpg Stage23 embryo oral cavity 02.jpg
Links: Carnegie stage 22 | Carnegie stage 23 | Week 8

Fetal

Week 10

Human week 10 fetus 04.jpg Section shows detail of the tongue muscular structure, formed from occipital somites.

The genioglossus (fan-shaped muscle) lies between the tongue and mandible and is innervated by the hypoglossal nerve (CN XII). Poking out your tongue is a test of this nerve. Note the tongue connective tissue and vasculature are derived from neural crest.

:Links: Week 10 | week 10 - sagittal section

Week 12 - 24

The following measurements of fetal tongue circumference show linear growth during the second trimester and are based upon multiple (2-10) separate ultrasound measurements.[10]

Fetal Tongue Circumference
Fertilisation Age
(weeks)
Gestational Age
GA (weeks)
Mean Circumference
(mm)
12 14 28
13 15 33
14 16 36
15 17 37
16 18 43
17 19 48
18 20 51
19 21 55
20 22 58
21 23 62
22 24 64
23 25 70
24 26 73
Table data[10] Tongue circumference measured by transvaginal ultrasonography between 14 and 17 GA weeks, and by abdominal ultrasound between 18 and 26 GA weeks of gestation.
Links: tongue | fetal | ultrasound

Tongue Muscles

  • Tongue muscles originate from the somites.
    • Masticatory muscles (MM) originate from the somitomeres. These muscles develop late and are not complete even at birth.
  • Tongue muscles develop before masticatory muscles and complete by birth.

Developing muscle fibers within the tongue. Note the multinucleated appearance of each muscle fiber and their overall organization. Muscle goes through the same developmental changes as other skeletal muscle.

See also: Embryonic and postnatal development of masticatory and tongue muscles.[11]

Skeletal muscle histology 017.jpg Skeletal muscle histology 018.jpg


Links: Skeletal Muscle Histology

Tongue Innervation

The tongue is innervated by a range of cranial nerve connections related to muscles, oral mucosa, taste buds, and minor salivary glands.

  • trigeminal nerve (CN V) - lingual branch
  • facial nerve (CN VII) - chorda tympani branch
  • glossopharyngeal nerve (CN IX)
  • hypoglossal nerve (CN XII) - motor components of innervated muscles.

The hypoglossal nerve (CN CN XII) provides the motor innervation of the intrinsic and extrinsic tongue muscles allowing protrusion, retrusion, and changes in the shape of the tongue. Motor units within the hypoglossal motor system can be categorized as predominantly fast fatigue resistant.[12]

The human tongue innervation has been recently analysed histologically and described as extremely dense and complex.[13] The structure of the motor endplate junctions (neuromuscular junctions) was found to be of the multiple en grappe (grapelike cluster) form. The transverse muscle group that comprises the core of the tongue was found to have the most complex innervation. The pattern of innervation of the human tongue also has specializations not found in other mammalian tongues, this allows for fine motor control of tongue shape.

The pathway of the hypoglossal nerve can be imaged using magnetic imaging (MRI) while computer tomography (CT) can show the bony anatomy of the neurovascular foramina of the skull base. Clinically, the nerve pathway can be divided into three regions: intra-axial, cisternal, skull base and extracranial segments.[14]


Links: Cranial Nerve Development

Lingual Frenulum

Inferior side of tongue with right side superficial dissection.

Frenulum is a general term for a small fold of integument (skin) or mucous membrane that limits the movements of an organ or part. There are several anatomical frenula associated with the genital system, while the lingual frenulum is associated with the inferior side of the tongue.

The lingual frenulum length (short) and position of insertion (anterior) can lead to speech disorders and may affect postnatal feeding.[15] Interestingly, it is the prevalence of pain in mothers breastfeeding infants with ankyloglossia that presents many problems in breastfeeding.[16]

Children with a frenulum length of more than 2 cm do not show these speech problems. Ankyloglossia (tongue-tie) is the general clinical term for the short frenulum which limits the range of movement of the tongue, there is still no accurate classification for this condition.[17] Frenotomy, frenectomy, and frenuloplasty are the main surgical treatment options to release or remove an ankyloglossia.

Histology

Abnormalities

Macroglossia

Macroglossia associated with congenital hypothyroidism.

Term means an abnormally large tongue. Macroglossia is more common than microglossia and can be associated with a number of genetic abnormalities including: trisomy 21 (Down syndrome), acromegaly, Beckwith-Wiedemann syndrome, mucopolysaccharidoses and primary amyloidosis. There is also an association with congenital hypothyroidism and diabetes.

Beckwith-Wiedemann syndrome macroglossia.jpg

Macroglossia associated with Beckwith-Wiedemann syndrome.

Links: Trisomy 21 | Medlineplus - Macroglossia

Microglossia

Term means an abnormally small tongue. A recent study has identified cranial neural crest fibroblasts non-canonical transforming growth factor β (TGFβ) regulation of FGF and BMP signalling can cause similar tongue muscle developmental defects.[5]

Ankyloglossia

Ankyloglossia (tongue-tie) is the general clinical term for the short lingual frenulum (less than 2 cm), that limits the range of movement of the tongue, prevalence ranges between 4.2% and 10.7%. This is associated with speech development disorders and has been suggested as also associated with feeding disorders. There is still no accurate classification for this condition.[17] Frenotomy, frenectomy, and frenuloplasty are the main surgical treatment options to release or remove an ankyloglossia, though there is still discussion about surgical intervention.

A short lingual frenulum is also associated with a number of genetic syndromes such as: ROR2-Related Robinow Syndrome, Dystrophic Epidermolysis Bullosa, Oral-Facial-Digital Syndrome Type I, Opitz Syndrome (X-Linked Opitz G/BBB Syndrome) and Van der Woude syndrome.


Links: Medline Plus - Tongue tie | ROR2-Related Robinow Syndrome | Dystrophic Epidermolysis Bullosa | Oral-Facial-Digital Syndrome Type I | X-Linked Opitz G/BBB Syndrome

Additional Images

Historic

Historic Disclaimer - information about historic embryology pages 
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Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Human Embryology and Morphology. Keith, A. (1902) London: Edward Arnold.

Anatomy of the Human Gray, H. (1918) Philadelphia: Lea & Febiger.

Text-Book of Embryology Bailey, F.R. and Miller, A.M. (1921). New York: William Wood and Co. - Tongue Development

References

  1. Okuhara S, Birjandi AA, Adel Al-Lami H, Sagai T, Amano T, Shiroishi T, Xavier GM, Liu KJ, Cobourne MT & Iseki S. (2019). Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature. Development , 146, . PMID: 31719045 DOI.
  2. Castillo-Azofeifa D, Seidel K, Gross L, Golden EJ, Jacquez B, Klein OD & Barlow LA. (2018). SOX2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis. Development , 145, . PMID: 29945863 DOI.
  3. Cobourne MT, Iseki S, Birjandi AA, Adel Al-Lami H, Thauvin-Robinet C, Xavier GM & Liu KJ. (2018). How to make a tongue: Cellular and molecular regulation of muscle and connective tissue formation during mammalian tongue development. Semin. Cell Dev. Biol. , , . PMID: 29784581 DOI.
  4. Zhu XJ, Yuan X, Wang M, Fang Y, Liu Y, Zhang X, Yang X, Li Y, Li J, Li F, Dai ZM, Qiu M, Zhang Z & Zhang Z. (2017). A Wnt/Notch/Pax7 signaling network supports tissue integrity in tongue development. J. Biol. Chem. , 292, 9409-9419. PMID: 28438836 DOI.
  5. 5.0 5.1 Iwata J, Suzuki A, Pelikan RC, Ho TV & Chai Y. (2013). Noncanonical transforming growth factor β (TGFβ) signaling in cranial neural crest cells causes tongue muscle developmental defects. J. Biol. Chem. , 288, 29760-70. PMID: 23950180 DOI.
  6. Song Z, Liu C, Iwata J, Gu S, Suzuki A, Sun C, He W, Shu R, Li L, Chai Y & Chen Y. (2013). Mice with Tak1 deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development. J. Biol. Chem. , 288, 10440-50. PMID: 23460641 DOI.
  7. Aoyama K, Yamane A, Suga T, Suzuki E, Fukui T & Nakamura Y. (2011). Bone morphogenetic protein-2 functions as a negative regulator in the differentiation of myoblasts, but not as an inducer for the formations of cartilage and bone in mouse embryonic tongue. BMC Dev. Biol. , 11, 44. PMID: 21736745 DOI.
  8. Kim JY, Lee MJ, Cho KW, Lee JM, Kim YJ, Kim JY, Jung HI, Cho JY, Cho SW & Jung HS. (2009). Shh and ROCK1 modulate the dynamic epithelial morphogenesis in circumvallate papilla development. Dev. Biol. , 325, 273-80. PMID: 19014928 DOI.
  9. Hong SJ, Cha BG, Kim YS, Lee SK & Chi JG. (2015). Tongue Growth during Prenatal Development in Korean Fetuses and Embryos. J Pathol Transl Med , 49, 497-510. PMID: 26471340 DOI.
  10. 10.0 10.1 Achiron R, Ben Arie A, Gabbay U, Mashiach S, Rotstein Z & Lipitz S. (1997). Development of the fetal tongue between 14 and 26 weeks of gestation: in utero ultrasonographic measurements. Ultrasound Obstet Gynecol , 9, 39-41. PMID: 9060129 DOI.
  11. Yamane A. (2005). Embryonic and postnatal development of masticatory and tongue muscles. Cell Tissue Res. , 322, 183-9. PMID: 16041600 DOI.
  12. Smith JC, Goldberg SJ & Shall MS. (2005). Phenotype and contractile properties of mammalian tongue muscles innervated by the hypoglossal nerve. Respir Physiol Neurobiol , 147, 253-62. PMID: 16087149 DOI.
  13. Mu L & Sanders I. (2010). Human tongue neuroanatomy: Nerve supply and motor endplates. Clin Anat , 23, 777-91. PMID: 20607833 DOI.
  14. Alves P. (2010). Imaging the hypoglossal nerve. Eur J Radiol , 74, 368-77. PMID: 20347541 DOI.
  15. Queiroz Marchesan I. (2004). Lingual frenulum: classification and speech interference. Int J Orofacial Myology , 30, 31-8. PMID: 15832860
  16. Segal LM, Stephenson R, Dawes M & Feldman P. (2007). Prevalence, diagnosis, and treatment of ankyloglossia: methodologic review. Can Fam Physician , 53, 1027-33. PMID: 17872781
  17. 17.0 17.1 Suter VG & Bornstein MM. (2009). Ankyloglossia: facts and myths in diagnosis and treatment. J. Periodontol. , 80, 1204-19. PMID: 19656020 DOI.

Reviews

Cobourne MT, Iseki S, Birjandi AA, Adel Al-Lami H, Thauvin-Robinet C, Xavier GM & Liu KJ. (2018). How to make a tongue: Cellular and molecular regulation of muscle and connective tissue formation during mammalian tongue development. Semin. Cell Dev. Biol. , , . PMID: 29784581 DOI.

Adameyko I & Fried K. (2016). The Nervous System Orchestrates and Integrates Craniofacial Development: A Review. Front Physiol , 7, 49. PMID: 26924989 DOI.

Parada C, Han D & Chai Y. (2012). Molecular and cellular regulatory mechanisms of tongue myogenesis. J. Dent. Res. , 91, 528-35. PMID: 22219210 DOI.

Articles

Michailovici I, Eigler T & Tzahor E. (2015). Craniofacial Muscle Development. Curr. Top. Dev. Biol. , 115, 3-30. PMID: 26589919 DOI.

Noden DM & Francis-West P. (2006). The differentiation and morphogenesis of craniofacial muscles. Dev. Dyn. , 235, 1194-218. PMID: 16502415 DOI.

Achiron R, Ben Arie A, Gabbay U, Mashiach S, Rotstein Z & Lipitz S. (1997). Development of the fetal tongue between 14 and 26 weeks of gestation: in utero ultrasonographic measurements. Ultrasound Obstet Gynecol , 9, 39-41. PMID: 9060129 DOI.

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Search PubMed: Tongue Development | Macroglossia | Microglossia

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Cite this page: Hill, M.A. (2024, March 19) Embryology Tongue Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Tongue_Development

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