Developmental Signals - Notch - Revision history

Z8600021 at 05:45, 9 March 2020

2020-03-09T05:45:09Z

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	===Reviews===		===Reviews===
			{{#pmid:32072495}}

	{{#pmid:23165243}}		{{#pmid:23165243}}

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			* '''Transitions in cell potency during early mouse development are driven by Notch'''{{#pmid:30958266\|PMID30958266}} "The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions."

	* '''Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning'''{{#pmid:27226324\|PMID27226324}} "Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning."		* '''Coordinated control of Notch/Delta signalling and cell cycle progression drives lateral inhibition-mediated tissue patterning'''{{#pmid:27226324\|PMID27226324}} "Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning."

	* '''Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors'''{{#pmid:25564622\|PMID25564622}} "Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation. This mechanism depends on the availability of Jag1 and Jag2, and is key to generating a population of parabasal cells that later activates Notch1 and Notch2 for secretory-multiciliated cell fate selection." [[Respiratory System Development]]		* '''Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors'''{{#pmid:25564622\|PMID25564622}} "Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation. This mechanism depends on the availability of Jag1 and Jag2, and is key to generating a population of parabasal cells that later activates Notch1 and Notch2 for secretory-multiciliated cell fate selection." [[Respiratory System Development]]

	* '''Notch regulation of myogenic versus endothelial fates of cells that migrate from the somite to the limb'''{{#pmid:24927569\|PMID24927569}} "Multipotent Pax3-positive (Pax3(+)) cells in the somites give rise to skeletal muscle and to cells of the vasculature. We had previously proposed that this cell-fate choice depends on the equilibrium between Pax3 and Foxc2 expression. In this study, we report that the Notch pathway promotes vascular versus skeletal muscle cell fates. ...We now demonstrate that in addition to the inhibitory role of Notch signaling on skeletal muscle cell differentiation, the Notch pathway affects the Pax3:Foxc2 balance and promotes the endothelial versus myogenic cell fate, before migration to the limb, in multipotent Pax3(+) cells in the somite of the mouse embryo." [[Musculoskeletal_System_-_Limb_Development\|Limb Development]] \| [[Musculoskeletal_System_-_Muscle_Development\|Muscle Development]]
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
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	Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Notch ''Notch'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Notch ''Notch'']

	~~<pubmed limit=5>Notch</pubmed>~~
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
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	\| {{Older papers}}		\| {{Older papers}}
			* '''Notch regulation of myogenic versus endothelial fates of cells that migrate from the somite to the limb'''{{#pmid:24927569\|PMID24927569}} "Multipotent Pax3-positive (Pax3(+)) cells in the somites give rise to skeletal muscle and to cells of the vasculature. We had previously proposed that this cell-fate choice depends on the equilibrium between Pax3 and Foxc2 expression. In this study, we report that the Notch pathway promotes vascular versus skeletal muscle cell fates. ...We now demonstrate that in addition to the inhibitory role of Notch signaling on skeletal muscle cell differentiation, the Notch pathway affects the Pax3:Foxc2 balance and promotes the endothelial versus myogenic cell fate, before migration to the limb, in multipotent Pax3(+) cells in the somite of the mouse embryo." [[Musculoskeletal_System_-_Limb_Development\|Limb Development]] \| [[Musculoskeletal_System_-_Muscle_Development\|Muscle Development]]

	* '''The precise timeline of transcriptional regulation reveals causation in mouse somitogenesis network'''{{#pmid:24304493\|PMID24304493}} "In vertebrate development, the segmental pattern of the body axis is established as somites, masses of mesoderm distributed along the two sides of the neural tube, are formed sequentially in the anterior-posterior axis. This mechanism depends on waves of gene expression associated with the Notch, Fgf and Wnt pathways."		* '''The precise timeline of transcriptional regulation reveals causation in mouse somitogenesis network'''{{#pmid:24304493\|PMID24304493}} "In vertebrate development, the segmental pattern of the body axis is established as somites, masses of mesoderm distributed along the two sides of the neural tube, are formed sequentially in the anterior-posterior axis. This mechanism depends on waves of gene expression associated with the Notch, Fgf and Wnt pathways."

Z8600021 at 00:25, 22 March 2018

2018-03-22T00:25:51Z

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	==Functions==		==Functions==

	Developmental patterning signal.		Developmental patterning signal.

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	{{Blastocyst Hippo table}}		{{Blastocyst Hippo table}}

	===Spinal Cord Development===		===Neural===
			====Spinal Cord Development====
	{\|		{\|
	\| Model of the embryonic rostro-caudal gradient of neurogenesis along the chicken spinal cord from the stem zone to the neurogenic neural tube summarising how DELTA-NOTCH signalling may be involved in these processes.{{#pmid:18000541\|PMID18000541}}		\| Model of the embryonic rostro-caudal gradient of neurogenesis along the chicken spinal cord from the stem zone to the neurogenic neural tube summarising how DELTA-NOTCH signalling may be involved in these processes.{{#pmid:18000541\|PMID18000541}}
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	\| [[File:Spinal cord delta notch model.png\|500px]]		\| [[File:Spinal cord delta notch model.png\|500px]]
	\|}		\|}
			====Hippocampus====

			'''Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment'''{{#pmid:28611114\|PMID28611114}}

			:"The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approach to selectively ablate Notch1 signaling in late immature precursors in the postnatal hippocampus by cross-breeding doublecortin (DCX)+ neuron-specific proopiomelanocortin (POMC)-α Cre mice with floxed Notch1 mice, we demonstrated a previously unreported pivotal role of Notch1 signaling in survival and function of adult newborn neurons in the dentate gyrus. Moreover, behavioral and functional studies demonstrated that POMC-Notch1-/- mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus."

			:'''Links:''' [[Neural - Hippocampus Development\|Hippocampus Development]]

	===Endoderm Development===		===Endoderm Development===

Z8600021 at 10:50, 21 March 2018

2018-03-21T10:50:03Z

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	==Notch Signaling==		==Notch Signaling==
	{\|		{\|
	\| [[File:Notch signaling pathway cartoon 02.jpg\|~~600px~~\|alt=Notch signaling pathway cartoon]]		\| [[File:Notch signaling pathway cartoon 02.jpg\|500px\|alt=Notch signaling pathway cartoon]]
			\|-
	\| Notch signaling pathway{{#pmid:19255248\|PMID19255248}}		\| Notch signaling pathway{{#pmid:19255248\|PMID19255248}}
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Z8600021 at 10:48, 21 March 2018

2018-03-21T10:48:10Z

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	===Mesoderm Development===		===Mesoderm Development===

	===~~Cartilage~~ Development===		===Blood Vessel Development===

			[[File:NOTCH-endothelial-cartoon.jpg\|600px]]

			NOTCH Signaling in the Endothelium{{#pmid:29547401PMID29547401}}

			(a) A vascular sprout is characterized by a leading ‘tip’ cell followed by ‘stalk’ cells.

			(b) Regulation of new sprouting during vascular expansion depends on integration of BMP signaling, NOTCH signaling and VEGF signaling.

			(c) In adult vessels, NOTCH is responsible for maintaining endothelial quiescence and junctional integrity.


	===Muscle Regeneration===		===Muscle Regeneration===

Z8600021 at 01:27, 21 March 2018

2018-03-21T01:27:09Z

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	===Early Development===		===Early Development===

	====Blastocyst===		====Blastocyst====

	{{Blastocyst Hippo table}}		{{Blastocyst Hippo table}}

Z8600021 at 01:26, 21 March 2018

2018-03-21T01:26:32Z

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	[[File:Notch structure cartoon.jpg\|thumb\|350px\|alt=Notch structure cartoon\|Notch structure cartoon{{#pmid:19255248\|PMID19255248}}]]		[[File:Notch structure cartoon.jpg\|thumb\|350px\|alt=Notch structure cartoon\|Notch structure cartoon{{#pmid:19255248\|PMID19255248}}]]
	The notch proteins were first identified in drosophila development and have since been identified as regulators of cell fate decisions during development. These are a family of cell surface transmembrane receptors that pass once through the plasma membrane.		The notch proteins were first identified in drosophila development and have since been identified as regulators of cell fate decisions during development. These are a family of cell surface transmembrane receptors that pass once through the plasma membrane.


			This signalling pathway is involved with many different developmental patterning pathways and in the adult is a key regulator in the vascular system.


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	\| [[File:Notch signaling pathway cartoon 02.jpg\|600px\|alt=Notch signaling pathway cartoon]]		\| [[File:Notch signaling pathway cartoon 02.jpg\|600px\|alt=Notch signaling pathway cartoon]]
	\| Notch signaling pathway{{#pmid:19255248\|PMID19255248}}		\| Notch signaling pathway{{#pmid:19255248\|PMID19255248}}
			\|-
	# Secretory pathway~~: the~~ modifications during the secretion of Notch to the membrane in the ER (purple) and the Golgi (orange). Notch is translated inside ER, where it is glycosylated by an O-fucosyltransferase O-Fut1 (light purple) and O-glucosyltransferase Rumi (yellow). Note the black circle on the Notch molecule in the ER; because Notch is not cleaved, the extracellular and intracellular domains are physically linked. Notch is then translocated into Golgi, where it is cleaved by Furin protease (scissors) at the S1 site and further modified by the N-acetylglucosaminyltransferase, Fringe. Note the red circle on the Notch molecule in the Golgi after S1 cleavage; the extracellular and intracellular domains are not physically linked		\|
	# Ligand-mediated activation: Notch (gray) interacts with the DSL ligands, Delta (blue) and Serrate (green), resulting in a series of proteolytic cleavage events induced by ligand binding. The S2 cleavage is mediated by ADAM protease (purple), whereas the S3/4 cleavage event is mediated by γ-secretase (g-secretase, in orange). Several studies also suggest that γ-secretase–mediated cleavage can occur inside endocytic compartment (shown in the light blue circle).		# '''Secretory pathway''' - modifications during the secretion of Notch to the membrane in the ER (purple) and the Golgi (orange). Notch is translated inside ER, where it is glycosylated by an O-fucosyltransferase O-Fut1 (light purple) and O-glucosyltransferase Rumi (yellow). Note the black circle on the Notch molecule in the ER; because Notch is not cleaved, the extracellular and intracellular domains are physically linked. Notch is then translocated into Golgi, where it is cleaved by Furin protease (scissors) at the S1 site and further modified by the N-acetylglucosaminyltransferase, Fringe. Note the red circle on the Notch molecule in the Golgi after S1 cleavage; the extracellular and intracellular domains are not physically linked
	# ~~The endocytic~~ regulation of ~~the~~ Notch receptor: full-length Notch can undergo endocytosis, leading to translocation of Notch into EEs, MVB, and lysosomes. From genetic data, several proteins have been identified to modulate this process, including Hrs and Bib, possibly during the EE-to-MVB transition of Notch, Lgd, and ESCRT complex, or during the MVB-to-lysosomes transition. These proteins further modulate Notch activity as described in the text. ~~The dotted~~ red arrow shows ~~that~~ in mutants ~~that~~ affect trafficking from the MVB to the lysosome, or if Notch is not trafficked to the lumen of the lysosome, Notch can undergo γ-secretase cleavage, resulting in a Notch GOF phenotypes.		# '''Ligand-mediated activation''' - Notch (gray) interacts with the DSL ligands, Delta (blue) and Serrate (green), resulting in a series of proteolytic cleavage events induced by ligand binding. The S2 cleavage is mediated by ADAM protease (purple), whereas the S3/4 cleavage event is mediated by γ-secretase (g-secretase, in orange). Several studies also suggest that γ-secretase–mediated cleavage can occur inside endocytic compartment (shown in the light blue circle).
			# '''Endocytic regulation of Notch receptor''' - full-length Notch can undergo endocytosis, leading to translocation of Notch into EEs, MVB, and lysosomes. From genetic data, several proteins have been identified to modulate this process, including Hrs and Bib, possibly during the EE-to-MVB transition of Notch, Lgd, and ESCRT complex, or during the MVB-to-lysosomes transition. These proteins further modulate Notch activity as described in the text. Dotted red arrow shows in mutants affect of trafficking from the MVB to the lysosome, or if Notch is not trafficked to the lumen of the lysosome, Notch can undergo γ-secretase cleavage, resulting in a Notch GOF phenotypes.

	(text from original figure legend)		(text from original figure legend)
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	{{Notch family collapsetable}}		{{Notch family collapsetable}}

			:Links: [https://www.genenames.org/cgi-bin/genefamilies/set/403 HGNC - Ankyrin repeat domain containing (ANKRD) gene family]

	===NOTCH3===		===NOTCH3===

Z8600021 at 00:57, 21 March 2018

2018-03-21T00:57:16Z

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			{{Notch family collapsetable}}

			===NOTCH3===

	* Notch3 activation retains mammary luminal cell in a nonproliferative state {{#pmid:24100291\|PMID24100291}}		* Notch3 activation retains mammary luminal cell in a nonproliferative state {{#pmid:24100291\|PMID24100291}}

Z8600021 at 00:56, 21 March 2018

2018-03-21T00:56:18Z

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	\|}		\|}
	==Notch Receptors==		==Notch Receptors==
			Notch receptors belong to the Ankyrin repeat domain containing (ANKRD) gene family (242 members).

	~~===NOTCH1===~~		{{Notch family table}}
	~~===NOTCH2===~~
	~~===NOTCH3===~~

	* Notch3 activation retains mammary luminal cell in a nonproliferative state.{{#pmid:24100291\|PMID24100291}}

			* Notch3 activation retains mammary luminal cell in a nonproliferative state {{#pmid:24100291\|PMID24100291}}
	===NOTCH4===		===NOTCH4===

Z8600021 at 00:34, 21 March 2018

2018-03-21T00:34:24Z

← Older revision		Revision as of 11:34, 21 March 2018
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	==Functions==		==Functions==
	Developmental patterning signal.		Developmental patterning signal.

			===Early Development===

			====Blastocyst===
			{{Blastocyst Hippo table}}

	===Spinal Cord Development===		===Spinal Cord Development===