Talk:2009 Lecture 15

Background Reading

Advances in early kidney specification, development and patterning. Dressler GR. Development. 2009 Dec;136(23):3863-74. PMID: 19906853

UNSW Embryology Related Pages

CD31, CD34 and FB21 - similar in endothelial cells after 25 weeks of gestation. alpha-SMA and nephrin - first observed in the S stage. maturation of endothelial cells starts at 25 weeks and is completed by 35 weeks of gestation. Epithelial cells and mesangial cells first appear during the S stage. PMID: 17464107

Computer Activities

UNSW Embryology: 2008 Science ANAT2341 - Embryology Lecture - Kidney Development | 2004 2004 Vertebrate Development Kidney slides (PDF 1 slide/page) | 2004 Kidney slides (PDF 4 slides/page) | 2004 Genital slides (PDF 1 slide/page) | 2004 Genital slides (PDF 4 slides/page)

Online resources

http://golgi.ana.ed.ac.uk/tutork.html

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2606293

Kidney Growth (size)

hin JS, Seo YS, Kim JH, Park KH. Nomogram of fetal renal growth expressed in length and parenchymal area derived from ultrasound images. J Urol. 2007 Nov;178(5):2150-4. Epub 2007 Sep 17.

PMID: 17870120

Cannie M, Neirynck V, De Keyzer F, Dymarkowski S, Bogaert GA. Prenatal magnetic resonance imaging demonstrates linear growth of the human fetal kidneys during gestation.

J Urol. 2007 Oct;178(4 Pt 2):1570-4. Epub 2007 Aug 16. PMID: 17707049 [PubMed - indexed for MEDLINE]

Although fetal kidneys have only 10% of their postnatal blood flow, fetal renal development is essential for normal postnatal function.

Bipolar length of the human fetal kidney increases at an average rate of 1.24 mm per week of gestation, while anteroposterior diameter increases at 0.57 mm per week of gestation between weeks 20 and 36. This indicates that bipolar diameter increases twice as rapidly as anteroposterior diameter.

This prenatal magnetic resonance imaging study demonstrates linear growth of the bipolar and anteroposterior diameters of human fetal kidneys in relation to gestational age. In addition, it is clear that bipolar diameter grows twice as rapidly as anteroposterior diameter and there is less variability for bipolar diameter. These normative curves may allow us to detect abnormal fetal evolution.

Glanc P, Umranikar S, Koff D, Tomlinson G, Chitayat D. Fetal sex assignment by sonographic evaluation of the pelvic organs in the second and third trimesters of pregnancy. J Ultrasound Med. 2007 May;26(5):563-9; quiz 570-1. PMID: 17459997 [PubMed - indexed for MEDLINE]

In the second trimester, measurements in 100% of male fetuses were less than 3.3 mm, and those in 94% of female fetuses were greater than 3.3 mm. In the third trimester, measurements in 96% of male fetuses were less than 4.7 mm, and those in 100% of female fetuses were greater than 4.7 mm. Ninety-eight percent of all fetuses with concave interfaces were female. The endometrium was visualized in 74%. The additional time per examination was less than 5 minutes in 87.7%. CONCLUSIONS: Internal pelvic fetal sex assignment is a reliable additional method for fetal sex determination. A numerical discriminatory level can be used to distinguish between male and female internal genitalia. Larger numbers will be required to further refine these values.

Nowak D, Góralczyk K, Zurada A, Gielecki J. Morphometrical analysis of the human suprarenal gland between the 4th and 7th months of gestation. Ann Anat. 2007;189(6):575-82. PMID: 18078001 [PubMed - indexed for MEDLINE]

The present study's purpose has been to examine the development of the human suprarenal glands (SGs) during the prenatal period. Special attention was paid to sexual dimorphism and the differences between the parameters of the right and left SGs. Specimens were obtained from 187 human fetuses spontaneously aborted between the 4th and 7th months of gestation. The SGs were dissected from the fetuses after an immersion and preservation period of 3-24 months in 9% formalin solution. The mass and linear dimensions of each isolated SG were obtained, and these data revealed a progressive two-fold increase between the 4th and 7th months of gestation. There was a gradual reduction in the ratio of the SG mass to the overall mass of the fetus with a marked decrease evident between the 4th and 5th months. Statistical analysis of both SGs showed significant differences between sexes in the mass and in the thickness of the left SG during the 5th and 6th months of gestation. Differences in the mass and linear dimensions of the left and right SGs were recorded from the 5th month of gestation to the 7th month. The mass and volume of the left SGs were higher than those on the right side. This allometric analysis provides data from a large sample of human fetuses and will later aid in microscopic and ultrasonographic studies.

Yigiter AB, Kavak ZN. Normal standards of fetal behavior assessed by four-dimensional sonography. J Matern Fetal Neonatal Med. 2006 Nov;19(11):707-21. PMID: 17127494 [PubMed - indexed for MEDLINE]

podocytes

Saleem MA, Zavadil J, Bailly M, McGee K, Witherden IR, Pavenstadt H, Hsu H, Sanday J, Satchell SC, Lennon R, Ni L, Bottinger EP, Mundel P, Mathieson PW. The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells. Am J Physiol Renal Physiol. 2008 Aug 6. [Epub ahead of print] PMID: 18684887

The glomerular podocyte is a highly specialised cell, with the ability to ultrafiltrate blood, and support glomerular capillary pressures. However, little is known about either the genetic programs leading to this functionality, or the final phenotype. We approached this question utilising a human conditionally immortalised cell line, which differentiate from a proliferating epithelial phenotype to a differentiated form. We profiled gene expression during several time points during differentiation, and grouped the regulated genes into major functional categories. A novel category of genes that was upregulated during differentiation was of smooth muscle related molecules. We further examined the smooth muscle phenotype and showed that podocytes consistently express the differentiated smooth muscle markers smoothelin, calponin and the specific transcription factor myocardin, both in vitro and in vivo. The contractile contribution of the podocyte to the glomerular capillary is controversial. We demonstrated using two novel techniques that podocytes contract vigorously in vitro, when differentiated, and in real-time were able to demonstrate angiotensin II treatment decreases monolayer resistance, morphologically correlating with enhanced contractility. We conclude that the mature podocyte in vitro possesses functional apparatus of contractile smooth muscle cells, with potential implications for its in vivo ability to regulate glomerular dynamic and permeability characteristics. Key words: mesenchyme, smoothelin, EMT, differentiation, development.

PMID: 18593568 [

Trb2 signals were detected in podocytes and the prospective mesangium of the glomeruli, as well as in ureteric bud tips

PMID: 17570939 The development of the filtration barrier is part of a complex sequence of steps proceeding from the early nephron anlage (renal vesicle) via the comma- and S-shaped body to the capillary loop stage and mature glomerulus. The main players are the podocytes (already in the stage of presumptive podocytes), which hold the commander function in this process, and the endothelial and the mesangial cells. A decisive role is also played by the GBM; its change in composition during the developmental process is a precondition for the final maturation of the podocytes, i.e. for the formation of the foot processes and, clearly subsequent, the slit membrane. Failure in the consecutive developmental stages due to genetic mutations or manipulations leads to characteristic hereditary diseases of increasing severity. The last step in this development, the formation of the slit membrane, marks a caesura between diseases with early and late onset; all disorders without a properly developed slit membrane start prenatally or at birth.

PMID: 17570939

Although the role of glomerular basement membrane has been emphasised as the barrier for retaining plasma proteins in the past three decades, some recent studies have demonstrated that the slit diaphragm of the glomerular epithelial cell (podocyte) is the structure likely to be the barrier in the glomerular capillary wall. Nephrin and podocin were identified as gene products mutated in Finnish-type congenital nephrotic syndrome and autosomal recessive steroid-resistant nephrotic syndrome, respectively. Nephrin s located at the outer leaflet of plasma membranes of the slit diaphragm. Podocin is reported to have an interaction with nephrin. The anti-nephrin antibody is capable of inducing massive proteinuria, which indicates that nephrin is a key functional molecule in the slit diaphragm. The expression of nephrin and podocin was reduced in glomeruli of minimal change nephrotic syndrome, which suggested that the altered expression of these molecules contributes to the development of proteinuria also in acquired diseases. Some recent studies demonstrated that CD2-associated protein (CD2AP) is also a functional molecule in the slit diaphragm, and its expression is altered in membranous nephropathy. These observations suggested that alteration of the molecular arrangement in the slit diaphragm is involved in the development of proteinuria in several kinds of glomerular diseases.

mesangial cell development

We propose a model in which mesangial cells originate from PDGF-Rbeta-positive progenitors surrounding the developing glomerular afferent and efferent arterioles, and are co-recruited in response to PDGF-B during angiogenic formation of the glomerular capillary tuft.

Glomerular capillaries consist of endothelial cells with large fenestrations, and are therefore very permeable ("leaky") for most solutes in blood plasma.

They provide structural support for and regulate blood flow of the glomerular capillaries by their contractile activity. The initiation of contraction of mesangial cells is similar to that of smooth muscle. Contraction of mesangial cells is coupled by that of basement membrane of the endothelium of glomerular capillaries, causing decrease in surface area of basement membrane. Thus, decreasing glomerular filtration rate.

They are also major contributors to the extracellular matrix which contains fibronectin, type IV collagen, perlecan, and laminin.

[edit] Phagocytosis

Mesangial cells also phagocytize glomerular basal lamina components and immunoglobulins. They are an unusual example of phagocytic cells derived from smooth muscle and not monocytes.