Tongue Development - Revision history

Z8600021 at 03:06, 23 February 2022

2022-02-23T03:06:41Z

← Older revision		Revision as of 13:06, 23 February 2022
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	==Introduction==		==Introduction==
	[[File:Fetal head section 04.jpg\|thumb\|alt=Fetal tongue (week 12)\|Fetal tongue (week 12)]]		[[File:Fetal head section 04.jpg\|thumb\|alt=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 {{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. The tongue has {{neural crest}} origins and muscle cells originate from and {{somites}} mesoderm, while the external muscles of mastication are derived from the unsegmented somitomeres. This current page gives a brief overview of early tongue development.

Z8600021 at 03:03, 23 February 2022

2022-02-23T03:03:01Z

← Older revision		Revision as of 13:03, 23 February 2022
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	* '''Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature'''{{#pmid:31719045\|PMID31719045}} "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 {{ME10.5}} 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."		* '''Mouse - Deletion of Nf2 in {{neural crest}}-derived {{tongue}} mesenchyme alters tongue shape and size, {{Hippo}} signalling and cell proliferation in a region- and stage-specific manner'''{{#pmid:34697858\|PMID34697858}} "The mammalian tongue develops from the branchial arches (1-4) and comprises highly organized tissues compartmentalized by mesenchyme/connective tissue that is largely derived from neural crest (NC). This study aimed to understand the roles of tumour suppressor Neurofibromin 2 (Nf2) in NC-derived tongue mesenchyme in regulating Hippo signalling and cell proliferation for the proper development of tongue shape and size. ...Specifically, at {{ME12.5}} Nf2cKO mutants had a decreased level of {{Hippo}} signalling transcription factor Yes-associated protein (Yap), Yap target genes and cell proliferation anteriorly, while having an increased Yap, Yap target genes and cell proliferation posteriorly, which lead to a tip-pointed and posteriorly widened tongue. At {{ME15.5}}, loss of Nf2 in the NC lineage resulted in distinct changes in cell proliferation in different regions, that is, high in epithelium and mesenchyme subjacent to the epithelium, and lower in deeper layers of the mesenchyme. At {{ME18.5}}, cell proliferation was reduced throughout the Nf2cKO tongue."

			* '''Temporospatial {{sonic hedgehog}} signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature'''{{#pmid:31719045\|PMID31719045}} "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 {{ME10.5}} 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."

	* '''{{SOX}}2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis'''{{#pmid:29945863\|PMID29945863}} "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}}		* '''{{SOX}}2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis'''{{#pmid:29945863\|PMID29945863}} "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}}

Z8600021 at 09:59, 26 December 2019

2019-12-26T09:59:49Z

← Older revision		Revision as of 19:59, 26 December 2019
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	===Reviews===		===Reviews===
			{{#pmid:29784581}}

	{{#pmid:26924989}}		{{#pmid:26924989}}

Z8600021 at 05:00, 23 December 2019

2019-12-23T05:00:13Z

← Older revision		Revision as of 15:00, 23 December 2019
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	{{Taste Links}}		{{Taste Links}}
			<br>
	{{gastrointestinal tract}} \| {{head}} \| [[:Category:Tongue\|Category:Tongue]]		{{gastrointestinal tract}} \| {{head}} \| [[:Category:Tongue\|Category:Tongue]]
			<br>
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
	! [[~~Embryology_History~~\|'''Historic Embryology''']]		! [[Historic Embryology Papers\|'''Historic Embryology''']] - Tongue
	\|-		\|-
	\| [[Book_-_Human_Embryology_and_Morphology_3#The_Tongue_and_its_Development\|1902 Tongue]] \| [[Paper - The development of the serous glands (von Ebner's) of the vallate papillae in man (1917)\|1917 von Ebner's glands]] \| [[Book_-_Text-Book_of_Embryology_12#The_Tongue\|1921 Tongue]]		\| [[Book_-_Human_Embryology_and_Morphology_3#The_Tongue_and_its_Development\|1902 Tongue]] \| [[Paper - The development of the serous glands (von Ebner's) of the vallate papillae in man (1917)\|1917 von Ebner's glands]] \| [[Book_-_Text-Book_of_Embryology_12#The_Tongue\|1921 Tongue]]

Z8600021 at 04:59, 23 December 2019

2019-12-23T04:59:09Z

← Older revision		Revision as of 14:59, 23 December 2019
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	! [[Embryology_History\|'''Historic Embryology''']]		! [[Embryology_History\|'''Historic Embryology''']]
	\|-		\|-
	\| [[Book_-_Human_Embryology_and_Morphology_3#The_Tongue_and_its_Development\|1902 Tongue]] \| [[Book_-_Text-Book_of_Embryology_12#The_Tongue\|1921 Tongue]]		\| [[Book_-_Human_Embryology_and_Morphology_3#The_Tongue_and_its_Development\|1902 Tongue]] \| [[Paper - The development of the serous glands (von Ebner's) of the vallate papillae in man (1917)\|1917 von Ebner's glands]] \| [[Book_-_Text-Book_of_Embryology_12#The_Tongue\|1921 Tongue]]
	\|}		\|}
	==Some Recent Findings==		==Some Recent Findings==

Z8600021 at 06:41, 21 November 2019

2019-11-21T06:41:38Z

← Older revision		Revision as of 16:41, 21 November 2019
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	\| Section shows detail of the tongue muscular structure, formed from occipital somites.		\| 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 (~~CN12~~). Poking out your tongue is a test of this nerve. Note the tongue connective tissue and vasculature are derived from neural crest.		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.
	\|}		\|}

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	==Tongue Innervation==		==Tongue Innervation==
	The tongue is innervated by a range of cranial nerve connections related to muscles, oral mucosa, taste buds, and minor salivary glands.		The tongue is innervated by a range of cranial nerve connections related to muscles, oral mucosa, taste buds, and minor salivary glands.
	* trigeminal nerve ({{~~CNV~~}}) - lingual branch		* trigeminal nerve ({{CN V}}) - lingual branch
	* facial nerve ({{~~CNVII~~}}) - chorda tympani branch		* facial nerve ({{CN VII}}) - chorda tympani branch
	* glossopharyngeal nerve ({{~~CNIX~~}})		* glossopharyngeal nerve ({{CN IX}})
	* hypoglossal nerve ({{~~CNXII~~}}) - motor components of innervated muscles.		* hypoglossal nerve ({{CN XII}}) - motor components of innervated muscles.

	The hypoglossal nerve (CN {{~~CNXII~~}}) 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.{{#pmid:16087149\|PMID16087149}}		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.{{#pmid:16087149\|PMID16087149}}

	The human tongue innervation has been recently analysed histologically and described as extremely dense and complex.{{#pmid:20607833\|PMID20607833}} 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 human tongue innervation has been recently analysed histologically and described as extremely dense and complex.{{#pmid:20607833\|PMID20607833}} 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.

Z8600021 at 06:39, 21 November 2019

2019-11-21T06:39:48Z

← Older revision		Revision as of 16:39, 21 November 2019
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	==Tongue Innervation==		==Tongue Innervation==
	The tongue is innervated by a range of cranial nerve connections related to muscles, oral mucosa, taste buds, and minor salivary glands.		The tongue is innervated by a range of cranial nerve connections related to muscles, oral mucosa, taste buds, and minor salivary glands.
	* trigeminal nerve (V) - lingual branch		* trigeminal nerve ({{CNV}}) - lingual branch
	* facial nerve (~~VII~~) - chorda tympani branch		* facial nerve ({{CNVII}}) - chorda tympani branch
	* glossopharyngeal nerve (IX)		* glossopharyngeal nerve ({{CNIX}})
	* hypoglossal nerve (~~XII~~) - motor components of innervated muscles.		* hypoglossal nerve ({{CNXII}}) - motor components of innervated muscles.

	The hypoglossal nerve (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.{{#pmid:16087149\|PMID16087149}}		The hypoglossal nerve (CN {{CNXII}}) 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.{{#pmid:16087149\|PMID16087149}}

	The human tongue innervation has been recently analysed histologically and described as extremely dense and complex.{{#pmid:20607833\|PMID20607833}} 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 human tongue innervation has been recently analysed histologically and described as extremely dense and complex.{{#pmid:20607833\|PMID20607833}} 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.

Z8600021 at 06:34, 21 November 2019

2019-11-21T06:34:09Z

← Older revision		Revision as of 16:34, 21 November 2019
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	* '''~~SOX2~~ regulation by hedgehog signaling controls adult lingual epithelium homeostasis'''{{#pmid:29945863\|PMID29945863}} "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}}		* '''Temporospatial sonic hedgehog signalling is essential for neural crest-dependent patterning of the intrinsic tongue musculature'''{{#pmid:31719045\|PMID31719045}} "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 {{ME10.5}} 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."

			* '''{{SOX}}2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis'''{{#pmid:29945863\|PMID29945863}} "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'''{{#pmid:29784581\|PMID29784581}} 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."		* '''Review - How to make a tongue: Cellular and molecular regulation of muscle and connective tissue formation during mammalian tongue development'''{{#pmid:29784581\|PMID29784581}} 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."

Z8600021 at 08:46, 11 Mayıs 2019

2019-05-11T08:46:32Z

← Older revision		Revision as of 18:46, 11 Mayıs 2019
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	* '''A {{Wnt}}/{{Notch}}/{{PAX}}7 signaling network supports tissue integrity in tongue development'''{{#pmid:28438836\|PMID28438836}} "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."		* '''A {{Wnt}}/{{Notch}}/{{PAX}}7 signaling network supports tissue integrity in tongue development'''{{#pmid:28438836\|PMID28438836}} "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."

	* '''Noncanonical transforming growth factor β ({{TGF-beta}}) signaling in cranial {{neural crest}} cells causes tongue muscle developmental defects'''{{#pmid:23950180\|PMID23950180}} "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."
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
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	\| [[File:Mark_Hill.jpg\|90px\|left]] {{Most_Recent_Refs}}		\| [[File:Mark_Hill.jpg\|90px\|left]] {{Most_Recent_Refs}}

	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Tongue+Embryology ''Tongue Embryology'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Tongue+Development ''Tongue Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Tongue+Embryology ''Tongue Embryology'']

	~~<pubmed limit=5>Tongue Embryology</pubmed>~~
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
	! Older papers		! Older papers
	\|-		\|-
	\|		\| {{Older papers}}
			* '''Noncanonical transforming growth factor β ({{TGF-beta}}) signaling in cranial {{neural crest}} cells causes tongue muscle developmental defects'''{{#pmid:23950180\|PMID23950180}} "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'''{{#pmid:23460641\|PMID23460641}} "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}}		* '''Mice with TGFβ activated kinase 1 (Tak1) deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development'''{{#pmid:23460641\|PMID23460641}} "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}}

Z8600021 at 05:36, 2 August 2018

2018-08-02T05:36:02Z

← Older revision		Revision as of 15:36, 2 August 2018
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			* '''SOX2 regulation by hedgehog signaling controls adult lingual epithelium homeostasis'''{{#pmid:29945863\|PMID29945863}} "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'''{{#pmid:29784581\|PMID29784581}} 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."		* '''Review - How to make a tongue: Cellular and molecular regulation of muscle and connective tissue formation during mammalian tongue development'''{{#pmid:29784581\|PMID29784581}} 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."