Endocrine - Pineal Development - Revision history

Z8600021 at 02:56, 5 April 2020

2020-04-05T02:56:20Z

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	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
	! Historic Pineal Papers		! Historic Pineal Papers
	\|-		\|-bgcolor="F5FFFA"
	\| [[Paper - On the pineal region in human embryos\|1917 Pineal Region]] \| [[Paper - The Human Pineal Gland and Pineal Cysts\|1932 Pineal Gland and Cysts]] \| [[Paper - Development and histogenesis of the human pineal organ (1935)\|1935 Pineal]] \| [[Paper - Development and histogenesis of the human pineal organ\|1937 Human Pineal]] \|		\| [[Paper - On the pineal region in human embryos\|1917 Pineal Region]] \| [[Paper - The Human Pineal Gland and Pineal Cysts\|1932 Pineal Gland and Cysts]] \| [[Paper - Development and histogenesis of the human pineal organ (1935)\|1935 Pineal]] \| [[Paper - Development and histogenesis of the human pineal organ\|1937 Human Pineal]] \| [[Paper - The nervous and vascular relations of the pineal gland (1940)\|1940 Nerve and Vascular Supply]]
	\|}		\|}
	<br>		<br>

Z8600021 at 22:21, 26 March 2020

2020-03-26T22:21:49Z

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	[[File:Pineal gland position.jpg\|thumb\|Pineal gland position]]		[[File:Pineal gland position.jpg\|thumb\|Pineal gland position]]

	The pineal gland (epiphysis cerebri) has an important role in the sleep/wake daily cycle (circadian), high melatonin plasma levels at nighttime and very low levels at daytime, and reproductive development. The gland is thought to evolutionarily to have been positioned as to be exposed to light, and hence remains a regulator of cyclic rhythms associated with day/night and day length. The pineal hormone (melatonin) has targets both in the nervous system and in many different peripheral tissues.		The pineal gland (epiphysis cerebri) has an important role in the sleep/wake daily cycle (circadian), high melatonin plasma levels at nighttime and very low levels at daytime, and reproductive development. The gland is thought to evolutionarily to have been positioned as to be exposed to light, and hence remains a regulator of cyclic rhythms associated with day/night and day length. The pineal hormone (melatonin) has targets both in the nervous system and in many different peripheral tissues. Melatonin synchronises circadian rhythms acting through the two G-protein-coupled receptors (MT1, MT2) in the suprachiasmatic nucleus of the {{hypothalamus}}.


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	* '''Infradian Rhythm of the Content of Secretory Granules in Pinealocyte Cytoplasm in Mice and Rats'''{{#pmid:29931631\|PMID29931631}} "The numerical density of secretory granules dense-core vesicles (DCV) in the cytoplasm of pinealocytes of the pineal gland was estimated by transmission electron microscopy in male white mice and Wistar rats. The 3-day biorhythm and lunaphase changes in the DCV content in the perikaryon and the processes of pinealocytes, which are manifested significantly in different seasons of the year, are established. The three-day biorhythm in adult male mice in comparison with younger male rats is not expressed uniformly in different phases of the moon. The in-phase manifestation of infradian biorhythms in different species of animals during the year with an unchanged daily photophase indicates the existence of common external synchronizers for mammals of these biorhythms that are not associated with the light/dark cycle." {{mouse}} \| {{rat}}		* '''Infradian Rhythm of the Content of Secretory Granules in Pinealocyte Cytoplasm in Mice and Rats'''{{#pmid:29931631\|PMID29931631}} "The numerical density of secretory granules dense-core vesicles (DCV) in the cytoplasm of pinealocytes of the pineal gland was estimated by transmission electron microscopy in male white mice and Wistar rats. The 3-day biorhythm and lunaphase changes in the DCV content in the perikaryon and the processes of pinealocytes, which are manifested significantly in different seasons of the year, are established. The three-day biorhythm in adult male mice in comparison with younger male rats is not expressed uniformly in different phases of the moon. The in-phase manifestation of infradian biorhythms in different species of animals during the year with an unchanged daily photophase indicates the existence of common external synchronizers for mammals of these biorhythms that are not associated with the light/dark cycle." {{mouse}} \| {{rat}}

	* '''Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator'''{{#pmid:27861587\|PMID27861587}} "The adult pineal gland is composed of pinealocytes, astrocytes, microglia, and other interstitial cells that have been described in detail. However, factors that contribute to pineal development have not been fully elucidated, nor have pineal cell lineages been well characterized. ...The pineal gland begins as an evagination of neuroepithelium in the roof of the third ventricle. The pineal primordium initially consists of radially aligned Pax6+ precursor cells that express vimentin and divide at the ventricular lumen. After the tubular neuroepithelium fuses, the distribution of ~~Pax6~~+ cells transitions to include rosette-like structures and later, dispersed cells. In the developing gland all dividing cells express Pax6, indicating that Pax6+ precursor cells generate pinealocytes and some interstitial cells. The density of Pax6+ cells decreases across pineal development as a result of cellular differentiation and microglial phagocytosis, but Pax6+ cells remain in the adult gland as a distinct population. Microglial colonization begins after pineal recess formation. Microglial phagocytosis of Pax6+ cells is not common at early stages but increases as microglia colonize the gland. In the postnatal gland microglia affiliate with Tuj1+ nerve fibers, IB4+ blood vessels, and Pax6+ cells. We demonstrate that microglia engulf Pax6+ cells, nerve fibers, and blood vessel-related elements, but not pinealocytes. We conclude that microglia play a role in pineal gland formation and homeostasis by regulating the precursor cell population, remodeling blood vessels and pruning sympathetic nerve fibers."		* '''Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator'''{{#pmid:27861587\|PMID27861587}} "The adult pineal gland is composed of pinealocytes, astrocytes, microglia, and other interstitial cells that have been described in detail. However, factors that contribute to pineal development have not been fully elucidated, nor have pineal cell lineages been well characterized. ...The pineal gland begins as an evagination of neuroepithelium in the roof of the {{third ventricle}}. The pineal primordium initially consists of radially aligned Pax6+ precursor cells that express vimentin and divide at the ventricular lumen. After the tubular neuroepithelium fuses, the distribution of {{Pax}}6+ cells transitions to include rosette-like structures and later, dispersed cells. In the developing gland all dividing cells express Pax6, indicating that Pax6+ precursor cells generate pinealocytes and some interstitial cells. The density of Pax6+ cells decreases across pineal development as a result of cellular differentiation and microglial phagocytosis, but Pax6+ cells remain in the adult gland as a distinct population. Microglial colonization begins after pineal recess formation. Microglial phagocytosis of Pax6+ cells is not common at early stages but increases as microglia colonize the gland. In the postnatal gland microglia affiliate with Tuj1+ nerve fibers, IB4+ blood vessels, and Pax6+ cells. We demonstrate that microglia engulf Pax6+ cells, nerve fibers, and blood vessel-related elements, but not pinealocytes. We conclude that microglia play a role in pineal gland formation and homeostasis by regulating the precursor cell population, remodeling blood vessels and pruning sympathetic nerve fibers."
	\|}		\|}
	{\| 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=Pineal+Embryology ''Pineal Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Development ''Pineal Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Melatonin+Embryology ''Melatonin Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Melatonin+Development ''Melatonin Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Hypoplasia ''Pineal Hypoplasia''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Tumour ''Pineal Tumour'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Embryology ''Pineal Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Development ''Pineal Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Melatonin+Embryology ''Melatonin Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Melatonin+Development ''Melatonin Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Melatonin+Receptor ''Melatonin Receptor''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Hypoplasia ''Pineal Hypoplasia''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Tumour ''Pineal Tumour'']
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
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	\| {{Older papers}}		\| {{Older papers}}

	* '''The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus'''{{#pmid:24647753\|PMID24647753}} "Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9 (-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9 (-/-) mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9 (-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9 (-/-)mutant mice, the neonatal pineal gland in these animals is hypo plastic."		* '''The Lhx9 homeobox gene controls pineal gland development and prevents postnatal {{hydrocephalus}}'''{{#pmid:24647753\|PMID24647753}} "Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9 (-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9 (-/-) mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9 (-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9 (-/-)mutant mice, the neonatal pineal gland in these animals is hypo plastic."

	* '''Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology'''{{#pmid:24132226\|PMID24132226}} "A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc. (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin."		* '''Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology'''{{#pmid:24132226\|PMID24132226}} "A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc. (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin."
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	==Melatonin==		==Melatonin==
	[[File:Melatonin.jpg\|thumb\|Melatonin molecular structure]]		[[File:Melatonin.jpg\|thumb\|Melatonin molecular structure]]
			Melatonin synchronises circadian rhythms through two G-protein-coupled receptors (MT1, MT2). Night release from the pineal gland activates melatonin receptors in the suprachiasmatic nucleus of the {{hypothalamus}}, this synchronises light–dark cycle of physiology and behaviour.


	* Melatonin is synthesized from the amino acid tryptophan within the pinealocytes.		* Melatonin is synthesized from the amino acid tryptophan within the pinealocytes.
	** Serotonin is first acetylated by aryl alkylamine N-acetyltransferase (AA-NAT), then converted to melatonin by acetyl serotonin methyl transferase (ASMT also known as hydroxyindole O-methyltransferase or HIOMT).		** Serotonin is first acetylated by aryl alkylamine N-acetyltransferase (AA-NAT), then converted to melatonin by acetyl serotonin methyl transferase (ASMT also known as hydroxyindole O-methyltransferase or HIOMT).
	* Melatonin release is stimulated by darkness and inhibited by light and is said to have neurological "chronobiotic" properties for resynchronization of sleep and circadian rhythms disturbances. In the periphery, melatonin is also involved in the regulation of several complex cycles: seasonal reproduction, body weight and energy balance.		* Melatonin release is stimulated by darkness and inhibited by light and is said to have neurological "chronobiotic" properties for resynchronization of sleep and circadian rhythms disturbances. In the periphery, melatonin is also involved in the regulation of several complex cycles: seasonal reproduction, body weight and energy balance.
	* Melatonin levels can be monitored by urinary excretion of the melatonin metabolite 6-sulfatoxymelatonin (aMT.6S).		* Melatonin levels can be monitored by urinary excretion of the melatonin metabolite 6-sulfatoxymelatonin (aMT.6S).



	'''Key Facts'''		'''Key Facts'''
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	===Melatonin Receptors===		===Melatonin Receptors===
	The hormone melatonin acts through receptors (high affinity G protein-coupled) embedded in the cell membrane. Three different receptor subtypes have been identified in mammals: MT1 (~~Mel 1a~~) and MT2 (~~Mel 1b~~) and a putative binding site called MT3.		The hormone melatonin acts through receptors (high affinity G protein-coupled) embedded in the cell membrane. Three different receptor subtypes have been identified in mammals: MT1 (MTNR1A) and MT2 (MTNR1B) and a putative binding site called MT3.

	* MT1 - expressed in humans in the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei of the hypothalamus.		* [https://www.omim.org/entry/600665 MT1] - ({{Chr4}}q35.2) expressed in humans in the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei of the hypothalamus.
	* MT2 - expressed in the retina.		* [https://www.omim.org/entry/600804 MT2] - ({{Chr11}}q14.3) expressed in the retina and brain.{{#pmid:7568007\|PMID7568007}}
	* MT3 - expressed in many non-mammalian vertebrates in a range of brain areas.		* MT3 - expressed in many non-mammalian vertebrates in a range of brain areas.

	:'''Links:''' [http://www.nature.com/nrd/journal/v9/n8/images/nrd3140-f2.jpg Image - melatonergic receptors coupled via Gαi]		:'''Links:''' [http://www.nature.com/nrd/journal/v9/n8/images/nrd3140-f2.jpg Image - melatonergic receptors coupled via Gαi]


	==Innervation==		==Innervation==
	The gland is connected to the hypothalamus suprachiasmatic nucleus (SCN) central rhythm generator through a multi-synaptic pathway.		The gland is connected to the hypothalamus suprachiasmatic nucleus (SCN) central rhythm generator through a multi-synaptic pathway.

Z8600021 at 22:43, 9 February 2020

2020-02-09T22:43:14Z

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	The embryo and fetus pineal does not produce significant amounts of melatonin, though has abundant tissue receptors. The maternal pineal gland produces melatonin in the normal circadian fashion and this melatonin can cross both the placenta and blood-brain barrier. In other species, maternal melatonin crosses the placenta into fetal circulation and may provide photoperiodic information during fetal development that influences later postnatal circadian (daily day/night) and seasonal (day length) rhythms. The pineals of non-mammalian vertebrates are photoreceptive, whereas those of mammals do not normally respond to directly light. Pineal blood supply is derived from the posterior cerebral artery choroidal branches and through the pineal recess is bathed in cerebrospinal fluid ({{CSF}}).		The embryo and fetus pineal does not produce significant amounts of melatonin, though has abundant tissue receptors. The maternal pineal gland produces melatonin in the normal circadian fashion and this melatonin can cross both the placenta and blood-brain barrier. In other species, maternal melatonin crosses the placenta into fetal circulation and may provide photoperiodic information during fetal development that influences later postnatal circadian (daily day/night) and seasonal (day length) rhythms. The pineals of non-mammalian vertebrates are photoreceptive, whereas those of mammals do not normally respond to directly light. Pineal blood supply is derived from the posterior cerebral artery choroidal branches and through the pineal recess is bathed in cerebrospinal fluid ({{CSF}}).


	The melatonin levels in premature infants is lower and delayed, but not different when calculated from conception date. Other factors such as preeclampsia, growth restriction, and nursery lighting can cause altered rhythm development. The same study has also shown that full-term infants born at home and full-term twins born in the hospital had significantly lower metabolite excretion levels than hospital-born singleton infants at the same ages despite similar body weights.{{#pmid:8636362\|PMID8636362}}		The melatonin levels in premature infants is lower and delayed, but not different when calculated from conception date. Other factors such as preeclampsia, growth restriction, and nursery lighting can cause altered rhythm development. The same study has also shown that full-term infants born at home and full-term twins born in the hospital had significantly lower metabolite excretion levels than hospital-born singleton infants at the same ages despite similar body weights.{{#pmid:8636362\|PMID8636362}} Allopregnanolone, a pineal neurosteroid, acts on the {{cerebellum}} supporting survival Purkinje cell by suppressing caspase-3 expression.{{#pmid:30339808\|PMID30339808}}

	Postnatally in humans, the melatonin levels may act on clock gene expression in the pars tuberalis of the {{anterior pituitary}} for photoperiodic switching. Melatonin also has important functions related to the program timing of {{puberty}}. Note that there are many clinical studies investigating the possible role of melatonin in diverse health areas, from oxygen starvation at birth through to neural effects in old age.		Postnatally in humans, the melatonin levels may act on clock gene expression in the pars tuberalis of the {{anterior pituitary}} for photoperiodic switching. Melatonin also has important functions related to the program timing of {{puberty}}. Note that there are many clinical studies investigating the possible role of melatonin in diverse health areas, from oxygen starvation at birth through to neural effects in old age.

Z8600021 at 22:38, 9 February 2020

2020-02-09T22:38:50Z

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	\|}		\|}

			* '''Bsx''' - homeobox gene-encoded transcription factor{{#pmid:31808568\|PMID31808568}}
	* '''Nodal''' - zebrafish required for dorsal convergence of pineal precursors.{{#pmid:17996054\|PMID17996054}}		* '''Nodal''' - zebrafish required for dorsal convergence of pineal precursors.{{#pmid:17996054\|PMID17996054}}
	* '''Pax6''' - rat pineal gland from E16, peak expression around E18.{{#pmid:23076630\|PMID23076630}}		* '''Pax6''' - rat pineal gland from E16, peak expression around E18.{{#pmid:23076630\|PMID23076630}}
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	* '''DARPP-32''' (Dopamine- and cAMP-regulated phosphoprotein of 32 kDa) is involved in the retinal pathway transmitting photic information that resets the circadian clock.		* '''DARPP-32''' (Dopamine- and cAMP-regulated phosphoprotein of 32 kDa) is involved in the retinal pathway transmitting photic information that resets the circadian clock.
	* OTX2, RAX, CRX, PAX4, TBX2B - also identified in development.		* OTX2, RAX, CRX, PAX4, TBX2B - also identified in development.


	'''Links:''' {{molecular}}		'''Links:''' {{molecular}}
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	===Articles===		===Articles===
			{{#pmid:31918071}}

	{{#pmid:27861587}}		{{#pmid:27861587}}

Z8600021 at 22:36, 9 February 2020

2020-02-09T22:36:29Z

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	~~Postnatally in humans, the~~ melatonin levels in premature infants is lower and delayed, but not different when calculated from conception date. Other factors such as preeclampsia, growth restriction, and nursery lighting can cause altered rhythm development. The same study has also shown that full-term infants born at home and full-term twins born in the hospital had significantly lower metabolite excretion levels than hospital-born singleton infants at the same ages despite similar body weights.{{#pmid:8636362\|PMID8636362}}		The melatonin levels in premature infants is lower and delayed, but not different when calculated from conception date. Other factors such as preeclampsia, growth restriction, and nursery lighting can cause altered rhythm development. The same study has also shown that full-term infants born at home and full-term twins born in the hospital had significantly lower metabolite excretion levels than hospital-born singleton infants at the same ages despite similar body weights.{{#pmid:8636362\|PMID8636362}}

			Postnatally in humans, the melatonin levels may act on clock gene expression in the pars tuberalis of the {{anterior pituitary}} for photoperiodic switching. Melatonin also has important functions related to the program timing of {{puberty}}. Note that there are many clinical studies investigating the possible role of melatonin in diverse health areas, from oxygen starvation at birth through to neural effects in old age.


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	* other activities - possibly gamete maturation, antioxidant effect, protect neurons?		* other activities - possibly gamete maturation, antioxidant effect, protect neurons?


	~~Note that there are many clinical studies investigating the possible role of melatonin in diverse health areas, from oxygen starvation at birth through to neural effects in old age.~~

	'''Links:''' {{pineal}} \| [[:Category:Pineal\|Category:Pineal]] \| [[Lecture - Endocrine Development]] \| [[Lecture - Head Development]]		'''Links:''' {{pineal}} \| [[:Category:Pineal\|Category:Pineal]] \| [[Lecture - Endocrine Development]] \| [[Lecture - Head Development]]
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	===Reviews===		===Reviews===
			{{#pmid31866317}}

	{{#pmid:30502386}}		{{#pmid:30502386}}

Z8600021 at 22:24, 9 February 2020

2020-02-09T22:24:40Z

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	Note that there are many clinical studies investigating the possible role of melatonin in diverse health areas, from oxygen starvation at birth through to neural effects in old age.		Note that there are many clinical studies investigating the possible role of melatonin in diverse health areas, from oxygen starvation at birth through to neural effects in old age.


	'''Links:''' {{pineal}} \| [[:Category:Pineal\|Category:Pineal]] \| [[Lecture - Endocrine Development]] \| [[Lecture - Head Development]]		'''Links:''' {{pineal}} \| [[:Category:Pineal\|Category:Pineal]] \| [[Lecture - Endocrine Development]] \| [[Lecture - Head Development]]

	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"
	! Historic Pineal Papers		! Historic Pineal Papers
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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=Pineal+Embryology ''Pineal Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Melatonin+Embryology ''Melatonin Embryology'']		Search term: [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Embryology ''Pineal Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Development ''Pineal Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Melatonin+Embryology ''Melatonin Development''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Melatonin+Development ''Melatonin Embryology''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Hypoplasia ''Pineal Hypoplasia''] \| [http://www.ncbi.nlm.nih.gov/pubmed/?term=Pineal+Tumour ''Pineal Tumour'']
	\|}		\|}
	{\| class="wikitable mw-collapsible mw-collapsed"		{\| class="wikitable mw-collapsible mw-collapsed"

Z8600021 at 22:21, 9 February 2020

2020-02-09T22:21:43Z

← Older revision		Revision as of 08:21, 10 February 2020
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	! Historic Pineal Papers		! Historic Pineal Papers
	\|-		\|-
	\| [[Paper - On the pineal region in human embryos\|1917 Pineal Region]] \| [[Paper - The Human Pineal Gland and Pineal Cysts\|1932 Pineal Gland and Cysts]] \| [[Paper - Development and histogenesis of the human pineal organ\|1937 Human Pineal]] \|		\| [[Paper - On the pineal region in human embryos\|1917 Pineal Region]] \| [[Paper - The Human Pineal Gland and Pineal Cysts\|1932 Pineal Gland and Cysts]] \| [[Paper - Development and histogenesis of the human pineal organ (1935)\|1935 Pineal]] \| [[Paper - Development and histogenesis of the human pineal organ\|1937 Human Pineal]] \|
	\|}		\|}
	<br>		<br>

Z8600021 at 12:55, 20 Mayıs 2019

2019-05-20T12:55:08Z

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	===Articles===		===Articles===

	{{#pmid:27861587}}		{{#pmid:27861587}}

			{{#pmid:25758643}}

	{{#pmid:19665543}}		{{#pmid:19665543}}

Z8600021 at 12:34, 20 Mayıs 2019

2019-05-20T12:34:20Z

← Older revision		Revision as of 22:34, 20 Mayıs 2019
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	===Articles===		===Articles===
			{{#pmid:27861587}}

	{{#pmid:19665543}}		{{#pmid:19665543}}

Z8600021 at 12:33, 20 Mayıs 2019

2019-05-20T12:33:16Z

← Older revision		Revision as of 22:33, 20 Mayıs 2019
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	===Reviews===		===Reviews===
			{{#pmid:30502386}}

	{{#pmid:30247830}}		{{#pmid:30247830}}