2014 Group Project 2 - Revision history

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2014-10-24T13:19:20Z

Protected "2014 Group Project 2" ([Edit=Allow only administrators] (indefinite) [Move=Allow only administrators] (indefinite))

← Older revision	Revision as of 23:19, 24 October 2014
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Z3465654: /* Current research models */

2014-10-24T06:17:32Z

Current research models

Z5030311: /* Current research models */

2014-10-24T06:09:08Z

Current research models

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 ==Current research models==
-Animals are good models to use when researching the development of the renal system as there are fewer ethical issues surrounding animals compared with humans and their generation time is much shorter so mutations can be identified much faster.
+Research is constantly being done on the development of the renal system; it is important to know what events happen at different stages of development and what initiates the different stages. The main events of development have been discovered so researchers now are looking at the development in more detail; for example looking at the origins of the structures, the impacts mothers have on their unborn child and ways to cure abnormalities. Animals are good models and are often used for research as there are fewer ethical issues surrounding them compared with humans and their generation time is much shorter so mutations can be identified faster. Below highlights a few of the recent studies that have been carried out to look at specific parts of renal development.
 [[File:Glomerular_number_in_Smoke_Exposed_offspring.png|300px|thumb|left|Glomerular number in Smoke Exposed and Control offspring]]
-Pringle et al. carried out a study and used lambs as their model in order to look at the affects and possible cures for Lower Urinary Tract Obstruction. Lower Urinary Tract Obstruction affects many newborns and is one of the most common causes of renal failure in young children. Therefore, it is important to find a way to prevent the damages to the renal system caused by the obstruction.
+'''The impact of maternal cigarette smoke exposure in a rodent model on renal development in the offspring'''<ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>
-A bladder obstruction was created in the lambs; this was done by ligating the urachus, 3 or 4 weeks after the obstruction was created shunts were put into the lambs so that the urine was able to bypass the obstruction; two different shunts were created, one had a valve and the other did not.
-The results found that the shunt without a valve resulted in the lamb foetus having a small, shrunken and thick-walled had poor function whereas the lambs with a valve shunt had a much better bladder function which was similar to the bladder without the shunt. This shows that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>
+-Mice have been used to determine the impact of maternal cigarette smoke exposure on the development of the renal system
 ==Kidney==

Z3465654: /* Developmental Timeline */

2014-10-24T05:31:31Z

Developmental Timeline

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	{\| class="wikitable"		{\| class="wikitable"
	\|-bgcolor="#9ACD32~~" align="centre~~"		\|- align="center" bgcolor="#9ACD32"
	\|'''Week''' \|\| '''Development'''		\|'''Week''' \|\| '''Development'''
	\|-bgcolor="#F0FFF0"		\|-bgcolor="#F0FFF0"

Z3465654: /* Kidney */

2014-10-24T05:19:58Z

Kidney

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	==Kidney==		==Kidney==
	[[File:Mouse Kidney Development Cartoon.jpg\|~~250px~~\|thumb\|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.\|left]]		[[File:Mouse Kidney Development Cartoon.jpg\|300px\|thumb\|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.\|left]]

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

Z3465654: /* Fetal Development */

2014-10-24T05:15:43Z

Fetal Development

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	'''Anatomical Position'''		'''Anatomical Position'''

	The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect <ref>Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623</ref><ref>Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier</ref>.		The kidneys initially begin to develop proximally to the pelvis, located at the level of the upper sacral segments. In order to attain the correct anatomical position, as the fetus develops, they continuously become more cranial in position until they reach the dorsal sides of the body at around the T12~L3 levels. This process is usually completed by week 9 of fetal development and occurs as a result of the kidneys coming into contact with the supra-adrenal glands, as well as due to the growth of the embryo’s body and abdominal cavity. These organs are medially rotated by up to ninety degrees during their ‘ascension’, so that the renal pelvis will lie on their medial aspect <ref name="Keeling & Kong, 2007">Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623</ref><ref>Moore: the developing human 9th edition. Saunders 2011. An imprint of Elsevier</ref>.

	During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys <ref>Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623</ref>.		During the entire process of anatomical positioning, the kidneys receive a bloody supply from arteries branching off at various points of the abdominal aorta. While they are initially vascularized by the lateral sacral branches of the aorta, during the ascent, they continue to receive blood at progressively higher levels. When the kidneys have achieved their correct position, they are supplied by the renal artery at the level of the 2nd lumbar vertebrae. The simultaneous rise of the vasculature helps to contribute to the ascending of the fetal kidneys <ref name="Keeling & Kong, 2007">Keeling, J.W. & Khong, T.Y. (2007). The Urinary System, Fetal and Neonatal Pathology. London: Springer. 4th Ed, pp. 623</ref>.

	[[Image:Ascension of the Kidneys.jpg\|500px\|thumb\|A hand drawn image of the ascension of the kidney.\|left]]		[[Image:Ascension of the Kidneys.jpg\|500px\|thumb\|A hand drawn image of the ascension of the kidney.\|left]]

Z3465654 at 05:06, 24 October 2014

2014-10-24T05:06:28Z

Show changes

Z5030311: /* Duplicated Ureter */

2014-10-24T05:05:15Z

Duplicated Ureter

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	[[File:Duplicated_ureter_.jpg\|400px\|thumb\|Duplicated Ureter]]		[[File:Duplicated_ureter_.jpg\|400px\|thumb\|Duplicated Ureter]]

	Duplicated ureters are the most common renal abnormality, estimated to occur in 1% of the total population, and is found to be more common in females and is a condition in which more than one ureter drains one kidney<ref> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref>. Ureteral duplications can be complete - in which the individual has two ureters from one kidney entering the bladder, or be incomplete, where there are two separate ureters leaving the one kidney that fuse into one tube before entering the bladder <ref name="PMID25313840"><pubmed>25313840</pubmed></ref>. Incomplete duplicated ureters often have no clinical significance other than a higher risk for urinary tract infections (UTI), however, completely duplicated ureters can present with some complications such as one of the ureters joining to the vagina or urethra instead of the bladder or to its complimentary duplicated ureter<ref><pubmed>9017803</pubmed></ref>.		Duplicated ureters are the most common renal abnormality, estimated to occur in 1% of the total population, and is found to be more common in females and is a condition in which more than one ureter drains one kidney<ref name="J.Gatti, 2013"> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref>. Ureteral duplications can be complete - in which the individual has two ureters from one kidney entering the bladder, or be incomplete, where there are two separate ureters leaving the one kidney that fuse into one tube before entering the bladder <ref name="PMID25313840"><pubmed>25313840</pubmed></ref>. Incomplete duplicated ureters often have no clinical significance other than a higher risk for urinary tract infections (UTI), however, completely duplicated ureters can present with some complications such as one of the ureters joining to the vagina or urethra instead of the bladder or to its complimentary duplicated ureter<ref><pubmed>9017803</pubmed></ref>.

	The development of the ureter begins at around 4 weeks into gestation when the ureteric bud branches from the Wolffian duct to extend into the nephrogenic blastema<ref> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref>. A study carried out on 30 children with duplicated ureters by Atwell et al. (1976) showed that 66% of children with an ureteral duplication had first degree relatives with either a complete or incompletely duplicated ureter, leading to the conclusion the defect is inherited in an autosomal dominant manner<ref><pubmed>1013379</pubmed></ref>.		The development of the ureter begins at around 4 weeks into gestation when the ureteric bud branches from the Wolffian duct to extend into the nephrogenic blastema<ref name="J.Gatti, 2013"> J. Gatti, J. Murphy, J. Williams, H. Koo (2013) emedicine overview, Ureteral Duplication, Ureteral Ectopia, and Ureterocele </ref>. A study carried out on 30 children with duplicated ureters by Atwell et al. (1976) showed that 66% of children with an ureteral duplication had first degree relatives with either a complete or incompletely duplicated ureter, leading to the conclusion the defect is inherited in an autosomal dominant manner<ref><pubmed>1013379</pubmed></ref>.

	==References==		==References==
	<references/>		<references/>

Z3465654: /* Kidney */

2014-10-24T03:51:27Z

Kidney

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	==Kidney==		==Kidney==
	[[File:Mouse Kidney Development Cartoon.jpg\|250px\|thumb\|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.\|left]]		[[File:Mouse Kidney Development Cartoon.jpg\|250px\|thumb\|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.\|left]]

	===Early Development===		===Early Development===
	The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref name="PMID24855634"><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref name="PMID24656820"><pubmed>24656820</pubmed></ref>. The following events occur:<ref name="PMID25088264"><pubmed>25088264</pubmed></ref>		The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref name="PMID24855634"><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref name="PMID24656820"><pubmed>24656820</pubmed></ref>. The following events occur:<ref name="PMID25088264"><pubmed>25088264</pubmed></ref>

Z3465654: /* Early Development */

2014-10-24T03:47:45Z

Early Development

← Older revision		Revision as of 13:47, 24 October 2014
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	[[File:Mouse Kidney Development Cartoon.jpg\|250px\|thumb\|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.\|left]]		[[File:Mouse Kidney Development Cartoon.jpg\|250px\|thumb\|The development of a mouse kidney from epithelial origin to fully formed. Although the timeframe is much shorter compared to a human, the same process of development applies.\|left]]
	===Early Development===		===Early Development===
	The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref name="PMID24855634"><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref name="PMID24656820"><pubmed>24656820</pubmed></ref>.		The kidneys first develop in the embryo by a process called nephrogenesis, in which self-renewing mesenchymal renal stem cells produce nephrons, the main functional unit, and form a simple embryonic kidney called the pronephros <ref name="PMID24855634"><pubmed>24855634</pubmed></ref>. This process of nephron formation is stimulated by the signaling between the ureteric buds and these stem cells, named progenitor cells and located at the tips of the ureteric buds, causing nephrons to develop and the ureteric buds to branch <ref name="PMID24656820"><pubmed>24656820</pubmed></ref>. The following events occur:<ref name="PMID25088264"><pubmed>25088264</pubmed></ref>

	~~When sufficient development has occurred during~~ week 3 ~~of gestation,~~ two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct. ~~As the~~ pronephri ~~continue to develop, they~~ elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct. ~~Towards the bottom of this duct, close to where it connects to the cloaca, is the~~ ureteric bud ~~connected by the ureter. Surrounding this bud is a mass of~~ metanephric mesoderm (blastema)~~, the two of which~~ react together to form the metanephros which goes on to form the mature kidney. The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli. This process ~~begins from as early as week 3 and continues until~~ week 8 of gestation~~. The~~ development of the nephrons ~~however,~~ continue through to week 32-36 ~~of gestation~~.~~<ref name="PMID25088264"><pubmed>25088264</pubmed></ref>~~		*During week 3 two pronephri are produced and nephrotomes, a series of tubules, begin to fuse together with the pronepheric duct.
			*The pronephri elongate and induce the nearby mesoderm to form mesonephri, and the pronepheric duct to become the mesonephric (Woffian) duct.
			*The ureteric bud and metanephric mesoderm (blastema) react together to form the metanephros which goes on to form the mature kidney.
			*The cells of the ureteric bud differentiate to form the major and minor calyces as well as the collecting tubules, while the cells of the metanephrogenic blastema develop into the renal tubules and glomeruli.
			*This process ends by week 8 of gestation, while the development of the nephrons continue through to week 32-36.

	===Fetal Development===		===Fetal Development===

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	'''The impact of maternal cigarette smoke exposure in a rodent model on renal development in the offspring'''<ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>		'''The impact of maternal cigarette smoke exposure in a rodent model on renal development in the offspring'''<ref name=”PMID25058584”><pubmed>25058584</pubmed></ref>

	-Mice have been used to determine the impact of maternal cigarette smoke exposure on the development of the renal system		*Mice have been used to determine the impact of maternal cigarette smoke exposure on the development of the renal system

	- It was predicted that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life		*It was predicted that smoke exposure would lead to a change in the expression of growth and transcription factors which would lead to kidney disease later on in life

	- An experiment found that there was up-regulation of some fibroblast growth factors and down-regulation of others which led to elayed nephron development and fewer nephrons present at birth		*An experiment found that there was up-regulation of some fibroblast growth factors and down-regulation of others which led to elayed nephron development and fewer nephrons present at birth

	-The image on the left shows left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood		*The image on the left shows left glomerular numbers in the control offspring are higher compared with smoke exposed offspring at birth, early postnatal period and adulthood

	-Glomerular in smoke exposed offspring were not mature and were not fully vascularised		*Glomerular in smoke exposed offspring were not mature and were not fully vascularised

	-Overall it was discovered that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood		*Overall it was discovered that cigarette smoke exposure during pregnancy and lactation period leads to underdeveloped renal system which can result in chronic kidney disorders in adulthood

	-As well as the impact of smoke exposure the effect of nicotine on development has been researched<ref name=”PMID25279991”><pubmed>25279991</pubmed></ref>		*As well as the impact of smoke exposure the effect of nicotine on development has been researched<ref name=”PMID25279991”><pubmed>25279991</pubmed></ref>

	'''Development of an animal model to study congenital urinary obstruction'''<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>		'''Development of an animal model to study congenital urinary obstruction'''<ref name=”PMID24013366”><pubmed>24013366</pubmed></ref>

	-Lambs were used to look at the possible cures for Lower Urinary Tract Obstruction		*Lambs were used to look at the possible cures for Lower Urinary Tract Obstruction

	-It’s important to find a cure for Lower Urinary Tract Obstruction as it affects many newborns and is one of the most common causes of renal failure in young children		*It’s important to find a cure for Lower Urinary Tract Obstruction as it affects many newborns and is one of the most common causes of renal failure in young children

	-Bladder obstructions were created in lambs by ligating the urachus		*Bladder obstructions were created in lambs by ligating the urachus

	-3 or 4 weeks after the obstruction was created shunts were placed in the lambs so the urine could bypass the obstruction		*3 or 4 weeks after the obstruction was created shunts were placed in the lambs so the urine could bypass the obstruction

	-Bypasses with and without valves were created		*Bypasses with and without valves were created

	-Shunts without valves led to small, shrunken and thick-walled bladders with poor function developing		*Shunts without valves led to small, shrunken and thick-walled bladders with poor function developing

	-Shunts with valves had much better bladder function		*Shunts with valves had much better bladder function

	-It was found that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.		*It was found that the cycle of filling and emptying the bladder with urine during foetal development is very important for the formation of the bladder.

	'''Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia''' <ref name=”PMID18061157”><pubmed>18061157</pubmed></ref>		'''Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia''' <ref name=”PMID18061157”><pubmed>18061157</pubmed></ref>

	-The fate of cap mesenchyme and pre-tubular aggregates that comprise the metanephric mesenchyme were investigated		*The fate of cap mesenchyme and pre-tubular aggregates that comprise the metanephric mesenchyme were investigated

	-Previous experiments have shown that metanephric mesenchyme gives rise to nephronic epithelial structures but it is not clear from which of the sub-populations, cap mesenchyme and pre-tubular aggregates, the structures arise.		*Previous experiments have shown that metanephric mesenchyme gives rise to nephronic epithelial structures but it is not clear from which of the sub-populations, cap mesenchyme and pre-tubular aggregates, the structures arise.

	-Transgenic mice were used with a mutation that allowed the fate of the transcriptional regulator, Cited1, only expressed in the cap mesenchyme to be followed.		*Transgenic mice were used with a mutation that allowed the fate of the transcriptional regulator, Cited1, only expressed in the cap mesenchyme to be followed.

	-It was found that collecting duct epithelium does not contain any cells originating from cap mesenchyme		*It was found that collecting duct epithelium does not contain any cells originating from cap mesenchyme

	-The cap mesenchyme was also found to have a population of epithelial progenitor cells that could self-renew.		*The cap mesenchyme was also found to have a population of epithelial progenitor cells that could self-renew.

	==Kidney==		==Kidney==