Talk:Respiratory System Development
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Cite this page: Hill, M.A. (2024, April 19) Embryology Respiratory System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Respiratory_System_Development |
10 Most Recent Papers
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Respiratory System Development
<pubmed limit=4>Respiratory System Development</pubmed>
2013
http://embryology.med.unsw.edu.au/Notes/respire.htm original page
Species Development of Fetal Lungs
| Gestational age (days) | |||||||
| Species | Term | Embryonic | Pseudoglandular | Canalicular | Saccular | ||
| Human | 280 | < 42 | 52 - 112 | 112 - 168 | 168 | ||
| Primate | 168 | < 42 | 57 - 80 | 80 - 140 | 140 | ||
| Sheep | 150 | < 40 | 40 - 80 | 80 - 120 | 120 | ||
| Rabbit | 32 | < 18 | 21 - 24 | 24 - 27 | 27 | ||
| Rat | 22 | < 13 | 16 - 19 | 19 - 20 | 21 | ||
| Mouse | 20 | < 9 | 16 | 18 | 19 | ||
<pubmed>10852845</pubmed>| PMC1637815 | Environ Health Perspect.
2012
Role of skeletal muscle in lung development
Histol Histopathol. 2012 Jul;27(7):817-26.
Baguma-Nibasheka M, Gugic D, Saraga-Babic M, Kablar B. Source Department of Anatomy and Neurobiology, Dalhousie University Faculty of Medicine, Halifax, Canada.
Abstract
Skeletal (striated) muscle is one of the four basic tissue types, together with the epithelium, connective and nervous tissues. Lungs, on the other hand, develop from the foregut and among various cell types contain smooth, but not skeletal muscle. Therefore, during earlier stages of development, it is unlikely that skeletal muscle and lung depend on each other. However, during the later stages of development, respiratory muscle, primarily the diaphragm and the intercostal muscles, execute so called fetal breathing-like movements (FBMs), that are essential for lung growth and cell differentiation. In fact, the absence of FBMs results in pulmonary hypoplasia, the most common cause of death in the first week of human neonatal life. Most knowledge on this topic arises from in vivo experiments on larger animals and from various in vitro experiments. In the current era of mouse mutagenesis and functional genomics, it was our goal to develop a mouse model for pulmonary hypoplasia. We employed various genetically engineered mice lacking different groups of respiratory muscles or lacking all the skeletal muscle and established the criteria for pulmonary hypoplasia in mice, and therefore established a mouse model for this disease. We followed up this discovery with systematic subtractive microarray analysis approach and revealed novel functions in lung development and disease for several molecules. We believe that our approach combines elements of both in vivo and in vitro approaches and allows us to study the function of a series of molecules in the context of lung development and disease and, simultaneously, in the context of lung's dependence on skeletal muscle-executed FBMs.
PMID 22648538
2011
The building blocks of mammalian lung development
Dev Dyn. 2011 Mar;240(3):463-76. doi: 10.1002/dvdy.22482. Epub 2010 Nov 18.
Rawlins EL.
Gurdon Institute and Department of Pathology, University of Cambridge, Cambridge, United Kingdom. e.rawlins@gurdon.cam.ac.uk.
Abstract Progress has recently been made in identifying progenitor cell populations in the embryonic lung. Some progenitor cell types have been definitively identified by lineage-tracing studies. However, others are not as well characterized and their existence is inferred on the basis of lung morphology, or mutant phenotypes. Here, I focus on lung development after the specification of the initial lung primordium. The evidence for various lung embryonic progenitor cell types is discussed and future experiments are suggested. The regulation of progenitor proliferation in the embryonic lung, and its coordinate control with morphogenesis, is also discussed. In addition, the relationship between embryonic and adult lung progenitors is considered. Developmental Dynamics 240:463-476, 2011. © 2010 Wiley-Liss, Inc.
Copyright © 2010 Wiley-Liss, Inc. PMID: 21337459
2010
Impact of environmental chemicals on lung development
Environ Health Perspect. 2010 Aug;118(8):1155-64. Epub 2010 May 5.
Miller MD, Marty MA.
Source
Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, California, USA. mmiller@oehha.ca.gov
Abstract
BACKGROUND:
Disruption of fundamental biologic processes and associated signaling events may result in clinically significant alterations in lung development.
OBJECTIVES:
We reviewed evidence on the impact of environmental chemicals on lung development and key signaling events in lung morphogenesis, and the relevance of potential outcomes to public health and regulatory science .
DATA SOURCES:
We evaluated the peer-reviewed literature on developmental lung biology and toxicology, mechanistic studies, and supporting epidemiology.
DATA SYNTHESIS:
Lung function in infancy predicts pulmonary function throughout life. In utero and early postnatal exposures influence both childhood and adult lung structure and function and may predispose individuals to chronic obstructive lung disease and other disorders. The nutritional and endogenous chemical environment affects development of the lung and can result in altered function in the adult. Studies now suggest that similar adverse impacts may occur in animals and humans after exposure to environmentally relevant doses of certain xenobiotics during critical windows in early life. Potential mechanisms include interference with highly conserved factors in developmental processes such as gene regulation, molecular signaling, and growth factors involved in branching morphogenesis and alveolarization.
CONCLUSIONS:
Assessment of environmental chemical impacts on the lung requires studies that evaluate specific alterations in structure or function-end points not regularly assessed in standard toxicity tests. Identifying effects on important signaling events may inform protocols of developmental toxicology studies. Such knowledge may enable policies promoting true primary prevention of lung diseases. Evidence of relevant signaling disruption in the absence of adequate developmental toxicology data should influence the size of the uncertainty factors used in risk assessments.
PMID 20444669
Epithelial N-cadherin and nuclear β-catenin are up-regulated during early development of human lung
Kaarteenaho R, Lappi-Blanco E, Lehtonen S.
BMC Dev Biol. 2010 Nov 16;10:113.
PMID 21080917 | PMC2995473 | BMC Dev Biol.
- Pseudoglandular period (weeks 12 to 16)
- E-cadherin was strongly expressed in all the epithelial cells of developing bronchi and bronchioles of all sizes including also the smallest structures
- N-cadherin was also moderately or strongly expressed in the epithelium of bronchi and largest bronchioles whereas it was negative in the smallest developing airways
- β-catenin displayed strong membrane-bound positivity in bronchi and larger bronchioles, whereas its expression in the small developing airways was mainly strongly nuclear.
- Canalicular period (weeks 16 to 28)
- Saccular (weeks 28 to 36) period
- Alveolar (weeks 36 to 40) period
Regulation of the pulmonary circulation in the fetus and newborn
Physiol Rev. 2010 Oct;90(4):1291-335.
Gao Y, Raj JU.
Department of Physiology and Pathophysiology, Peking University, Health Science Center, Beijing, China. Abstract During the development of the pulmonary vasculature in the fetus, many structural and functional changes occur to prepare the lung for the transition to air breathing. The development of the pulmonary circulation is genetically controlled by an array of mitogenic factors in a temporo-spatial order. With advancing gestation, pulmonary vessels acquire increased vasoreactivity. The fetal pulmonary vasculature is exposed to a low oxygen tension environment that promotes high intrinsic myogenic tone and high vasocontractility. At birth, a dramatic reduction in pulmonary arterial pressure and resistance occurs with an increase in oxygen tension and blood flow. The striking hemodynamic differences in the pulmonary circulation of the fetus and newborn are regulated by various factors and vasoactive agents. Among them, nitric oxide, endothelin-1, and prostaglandin I(2) are mainly derived from endothelial cells and exert their effects via cGMP, cAMP, and Rho kinase signaling pathways. Alterations in these signaling pathways may lead to vascular remodeling, high vasocontractility, and persistent pulmonary hypertension of the newborn.
PMID 20959617
Preparing for the first breath: genetic and cellular mechanisms in lung development
Dev Cell. 2010 Jan 19;18(1):8-23.
Morrisey EE, Hogan BL.
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. emorrise@mail.med.upenn.edu
Abstract The mammalian respiratory system--the trachea and the lungs--arises from the anterior foregut through a sequence of morphogenetic events involving reciprocal endodermal-mesodermal interactions. The lung itself consists of two highly branched, tree-like systems--the airways and the vasculature--that develop in a coordinated way from the primary bud stage to the generation of millions of alveolar gas exchange units. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as branching morphogenesis, vascular development, and the differentiation of multipotent progenitor populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding respiratory disorders, congenital defects in human neonates, and how the disruption of morphogenetic programs early in lung development can lead to deficiencies that persist throughout life.
PMID 20152174
2009
Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut
Dev Cell. 2009 Aug;17(2):290-8.
Goss AM, Tian Y, Tsukiyama T, Cohen ED, Zhou D, Lu MM, Yamaguchi TP, Morrisey EE. Source Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abstract
Patterning of the primitive foregut promotes appropriate organ specification along its anterior-posterior axis. However, the molecular pathways specifying foregut endoderm progenitors are poorly understood. We show here that Wnt2/2b signaling is required to specify lung endoderm progenitors within the anterior foregut. Embryos lacking Wnt2/2b expression exhibit complete lung agenesis and do not express Nkx2.1, the earliest marker of the lung endoderm. In contrast, other foregut endoderm-derived organs, including the thyroid, liver, and pancreas, are correctly specified. The phenotype observed is recapitulated by an endoderm-restricted deletion of beta-catenin, demonstrating that Wnt2/2b signaling through the canonical Wnt pathway is required to specify lung endoderm progenitors within the foregut. Moreover, activation of canonical Wnt/beta-catenin signaling results in the reprogramming of esophagus and stomach endoderm to a lung endoderm progenitor fate. Together, these data reveal that canonical Wnt2/2b signaling is required for the specification of lung endoderm progenitors in the developing foregut.
PMID: 19686689
Growth of the lung parenchyma early in life
Am J Respir Crit Care Med. 2009 Jan 15;179(2):134-7. Epub 2008 Nov 7.
Balinotti JE, Tiller CJ, Llapur CJ, Jones MH, Kimmel RN, Coates CE, Katz BP, Nguyen JT, Tepper RS.
Source
Department of Pediatrics, Indiana University Medical Center, James Whitcomb Riley Hospital for Children, Herman B. Wells Center for Pediatric Research, Indianapolis, Indiana 46202-5225, USA.
Abstract
RATIONALE: Early in life, lung growth can occur by alveolarization, an increase in the number of alveoli, as well as expansion. We hypothesized that if lung growth early in life occurred primarily by alveolarization, then the ratio of pulmonary diffusion capacity of carbon monoxide (Dl(CO)) to alveolar volume (V(A)) would remain constant; however, if lung growth occurred primarily by alveolar expansion, then Dl(CO)/V(A) would decline with increasing age, as observed in older children and adolescents. OBJECTIVES: To evaluate the relationship between alveolar volume and pulmonary diffusion capacity early in life. METHODS: In 50 sleeping infants and toddlers, with equal number of males and females between the ages of 3 and 23 months, we measured Dl(CO) and V(A) using single breath-hold maneuvers at elevated lung volumes. MEASUREMENTS AND MAIN RESULTS: Dl(CO) and V(A) increased with increasing age and body length. Males had higher Dl(CO) and V(A) when adjusted for age, but not when adjusted for length. Dl(CO) increased with V(A); there was no gender difference when Dl(CO) was adjusted for V(A). The ratio of Dl(CO)/V(A) remained constant with age and body length. CONCLUSIONS: Our results suggest that surface area for diffusion increases proportionally with alveolar volume in the first 2 years of life. Larger Dl(CO) and V(A) for males than females when adjusted for age, but not when adjusted for length, is primarily related to greater body length in boys. The constant ratio for Dl(CO)/V(A) in infants and toddlers is consistent with lung growth in this age occurring primarily by the addition of alveoli rather than the expansion of alveoli.
PMID 18996997
2008
Evidence and structural mechanism for late lung alveolarization
Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L246-54. Epub 2007 Nov 21.
Schittny JC, Mund SI, Stampanoni M. Source Institute of Anatomy, University of Bern, Baltzerstrasse 2, Bern, Switzerland. johannes.schittny@ana.unibe.ch
Abstract
According to the current view, the formation of new alveolar septa from preexisting ones ceases due to the reduction of a double- to a single-layered capillaries network inside the alveolar septa (microvasculature maturation postnatal days 14-21 in rats). We challenged this view by measuring stereologically the appearance of new alveolar septa and by studying the alveolar capillary network in three-dimensional (3-D) visualizations obtained by high-resolution synchrotron radiation X-ray tomographic microscopy. We observed that new septa are formed at least until young adulthood (rats, days 4-60) and that roughly half of the new septa are lifted off of mature septa containing single-layered capillary networks. At the basis of newly forming septa, we detected a local duplication of the capillary network. We conclude that new alveoli may be formed in principle at any time and at any location inside the lung parenchyma and that lung development continues into young adulthood. We define two phases during developmental alveolarization. Phase one (days 4-21), lifting off of new septa from immature preexisting septa, and phase two (day 14 through young adulthood), formation of septa from mature preexisting septa. Clinically, our results ask for precautions using drugs influencing structural lung development during both phases of alveolarization.
PMID 18032698
2006
Structural aspects of postnatal lung development - alveolar formation and growth
Biol Neonate. 2006;89(4):313-22. Epub 2006 Jun 1.
Burri PH. Source Institute of Anatomy, University of Berne, Berne, Switzerland. burri@ana.unibe.ch
Abstract
The human lung is born with a fraction of the adult complement of alveoli. The postnatal stages of human lung development comprise an alveolar stage, a stage of microvascular maturation, and very likely a stage of late alveolarization. The characteristic structural features of the alveolar stage are well known; they are very alike in human and rat lungs. The bases for alveolar formation are represented by immature inter-airspace walls with two capillary layers with a central sheet of connective tissue. Interalveolar septa are formed by folding up of one of the two capillary layers. In the alveolar stage, alveolar formation occurs rapidly and is typically very conspicuous in both species; it has therefore been termed 'bulk alveolarization'. During and after alveolarization the septa with double capillary networks are restructured to the mature form with a single network. This happens in the stage of microvascular maturation. After these steps the lung proceeds to a phase of growth during which capillary growth by intussusception plays an important role in supporting gas exchange. In view of reports that alveoli are added after the stage of microvascular maturation, the question arises whether the present concept of alveolar formation needs revision. On the basis of morphological and experimental findings we can state that mature lungs contain all the features needed for 'late alveolarization' by the classical septation process. Because of the high plasticity of the lung tissues, late alveolarization or some forms of compensatory alveolar formation may be considered for the human lung. Copyright (c) 2006 S. Karger AG, Basel.
PMID 16770071
2003
Lung growth and development
Front Biosci. 2003 Jan 1;8:d392-415.
Chinoy MR.
Lung Development Research Program, Department of Surgery, Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033-0850, USA. mchinoy@psu.edu Abstract The organogenesis of lung involves several complex mechanisms, including interactions between cells originating from two germ layers--endoderm and mesoderm. Regulation of lung branching morphogenesis with reference to its architecture, growth pattern, differentiation, interactions between epithelium and mesenchyme and / or endothelium, as well as genes regulating these processes have been addressed by the pulmonary biologists through careful molecular biology and genetic experimental approaches. The mammalian lung develops by outpouching from the foregut endoderm as two lung buds into the surrounding splanchnic mesenchyme. Several different regions of the foregut are specified to develop into different thoracic and visceral organs. The lung-buds further elongate and branch, and the foregut longitudinally gets separated into esophagus and trachea. In rodents (mice and rats), this occurs around embryonic day 11, where the right lung bud develops into four different lobes and left lung develops as a single lobe. In humans, these processes occur by 3-4 weeks of embryonic development, where the right lung is a trilobar lung and the left lung is a bilobar lung. Several generations of dichotomous branching occur during embryonic development, followed by secularization and alveolarization pre- and post-natally, which transform a fluid-filled lung into an air-breathing lung able to sustain the newborn. During these different developmental stages from embryonic to newborn stage, the lung architecture undergoes profound changes, which are marked by a series of programmed events regulated by master genes (e.g., homeobox genes), nuclear transcription factors, hormones, growth factors and other factors. These programmed events can be altered by undesirable exposure to overdoses of hormones/vitamins/growth factors, synthetic drugs, environmental toxins, radiation and other agents. In the recent years molecular techniques have opened avenues to study specific functions of genes or their products (proteins) in vivo or in vitro at a cellular or an organelle level, some of these include targeted disruption, knock-in / knock-out genes, in vitro mutagenesis, use of sense and anti-sense oligonucleotides. Some of these aspects with reference to regulation of normal lung development and growth and a specific example of pulmonary hypoplasia as an abnormal lung formation are discussed in this review.
PMID: 12456356
http://www.ncbi.nlm.nih.gov/pubmed/12456356
2002
Airway and blood vessel interaction during lung development
J Anat. 2002 Oct;201(4):325-34.
Hislop AA. Source Unit of Vascular Biology and Pharmacology, Institute of Child Health, London, UK. A.Hislop@ich.ucl.ac.uk
Abstract
In the adult lung the pulmonary arteries run alongside the airways and the pulmonary veins show a similar branching pattern to the arteries, though separated from them. During early fetal development the airways act as a template for pulmonary blood vessel development in that the vessels form by vasculogenesis around the branching airways. In later lung development the capillary bed is essential for alveolar formation. This paper reviews evidence for the interaction of the airways and blood vessels in both normal and abnormal lung development.
PMID 12430957
Origin, differentiation, and maturation of human pulmonary veins
Am J Respir Cell Mol Biol. 2002 Mar;26(3):333-40.
Hall SM, Hislop AA, Haworth SG.
Unit of Vascular Biology and Pharmacology, Institute of Child Health, University College, London, United Kingdom. S.Hall@ich.ucl.ac.uk Abstract Recent studies on human embryonic and fetal lungs show that the pulmonary arteries form by vasculogenesis. Little is known of the early development of the pulmonary veins. Using immunohistochemical techniques and serial reconstruction, we studied 18 fetal and neonatal lungs. Sections were stained with antibodies specific for endothelium (CD31, von Willebrand factor) and smooth muscle (alpha and gamma smooth muscle actin, smooth muscle myosin, calponin, caldesmon, and desmin) and antibodies specific for the matrix glycoprotein tenascin, the receptor protein tyrosine kinase EphB4, and its ligand ephrinB2. Kiel University-raised antibody number 67 (Ki67) expression allowed qualitative assessment of cell replication. By 34 d gestation, there was continuity between the aortic sac, pulmonary arteries, capillaries, pulmonary veins, and atrium. The pulmonary veins formed by vasculogenesis in the mesenchyme surrounding the terminal buds during the pseudoglandular period and probably by angiogenesis in the canalicular and alveolar stages. EphB4 and ephrinB2 did not distinguish between presumptive venous and arterial endothelium as they do in mouse. All venous smooth muscle cells derived directly from the mesenchyme, gradually acquiring smooth muscle specific proteins from 56 d gestation. Thus, both pulmonary arteries and veins arise by vasculogenesis, but the origins of their smooth muscle cells and their cytoskeletal protein content are different.
PMID 11867341
http://ajrcmb.atsjournals.org/cgi/content/full/26/3/333
Invited review: Clearance of lung liquid during the perinatal period
J Appl Physiol. 2002 Oct;93(4):1542-8.
Barker PM, Olver RE.
Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599-7220, USA. pbarker@med.unc.edu
Abstract
At birth, the distal lung epithelium undergoes a profound phenotypic switch from secretion to absorption in the course of adaptation to air breathing. In this review, we describe the developmental regulation of key membrane transport proteins and the way in which epinephrine, oxygen, glucocorticoids, and thyroid hormones interact to bring about this crucial change in function. Evidence from molecular, transgenic, cell culture, and whole lung studies is presented, and the clinical consequences of the failure of the physiological mechanisms that underlie perinatal lung liquid absorption are discussed.
PMID 12235057
http://jap.physiology.org/cgi/content/full/93/4/1542
2000
Prenatal origins of human intrapulmonary arteries: formation and smooth muscle maturation
Am J Respir Cell Mol Biol. 2000 Aug;23(2):194-203.
Hall SM, Hislop AA, Pierce CM, Haworth SG.
Unit of Vascular Biology and Pharmacology, Cardiovascular and Respiratory Sciences, Institute of Child Health, University College of London, London, United Kingdom.
Abstract Recent studies on the morphogenesis of the pulmonary arteries have focused on nonhuman species such as the chick and the mouse. Using immunohistochemical techniques, we have studied 16 lungs from human embryos and fetuses from 28 d of gestation to newborn, using serial sections stained with a panel of antibodies specific for endothelium, smooth muscle, and extracellular matrix proteins. Cell replication was also assessed. Serial reconstruction showed a continuity of circulation between the heart and the capillary plexus from at least 38 d of gestation. The intrapulmonary arteries appeared to be derived from a continuous expansion of the primary capillary plexus that is from within the mesenchyme, by vasculogenesis. The arteries formed by continuous coalescence of endothelial tubes alongside the newly formed airway. Findings were consistent with the pulmonary arterial smooth muscle cells being derived from three sites in a temporally distinct sequence: the earliest from the bronchial smooth muscle, later from the mesenchyme surrounding the arteries, and last from the endothelial cells. Despite their different origins, all smooth muscle cells followed the same sequence of expression of smooth muscle-specific cytoskeletal proteins with increasing age. The order of appearance of these maturing proteins was from the subendothelial cells outward across the vessel wall and from hilum to periphery. The airways would seem to act as a template for pulmonary artery development. This study provides a framework for studying the signaling mechanisms controlling the various aspects of lung development.
intrapulmonary arteries
- appeared to be derived from a continuous expansion of the primary capillary plexus from within the mesenchyme, by vasculogenesis.
- arteries formed by continuous coalescence of endothelial tubes alongside the newly formed airway.
pulmonary arterial smooth muscle cells derived from three sites in a temporally distinct sequence
- earliest from the bronchial smooth muscle
- from the mesenchyme surrounding the arteries
- last from the endothelial cells.
- all smooth muscle cells followed the same sequence of expression of smooth muscle-specific cytoskeletal proteins with increasing age.
- order of appearance of these maturing proteins was from the subendothelial cells outward across the vessel wall and from hilum to periphery.
The airways would seem to act as a template for pulmonary artery development.
PMID: 10919986 http://www.ncbi.nlm.nih.gov/pubmed/10919986
http://ajrcmb.atsjournals.org/cgi/content/full/23/2/194
Prenatal origins of human intrapulmonary arteries: formation and smooth muscle maturation
Am J Respir Cell Mol Biol. 2000 Aug;23(2):194-203.
Hall SM, Hislop AA, Pierce CM, Haworth SG.
Source
Unit of Vascular Biology and Pharmacology, Cardiovascular and Respiratory Sciences, Institute of Child Health, University College of London, London, United Kingdom.
Abstract
Recent studies on the morphogenesis of the pulmonary arteries have focused on nonhuman species such as the chick and the mouse. Using immunohistochemical techniques, we have studied 16 lungs from human embryos and fetuses from 28 d of gestation to newborn, using serial sections stained with a panel of antibodies specific for endothelium, smooth muscle, and extracellular matrix proteins. Cell replication was also assessed. Serial reconstruction showed a continuity of circulation between the heart and the capillary plexus from at least 38 d of gestation. The intrapulmonary arteries appeared to be derived from a continuous expansion of the primary capillary plexus that is from within the mesenchyme, by vasculogenesis. The arteries formed by continuous coalescence of endothelial tubes alongside the newly formed airway. Findings were consistent with the pulmonary arterial smooth muscle cells being derived from three sites in a temporally distinct sequence: the earliest from the bronchial smooth muscle, later from the mesenchyme surrounding the arteries, and last from the endothelial cells. Despite their different origins, all smooth muscle cells followed the same sequence of expression of smooth muscle-specific cytoskeletal proteins with increasing age. The order of appearance of these maturing proteins was from the subendothelial cells outward across the vessel wall and from hilum to periphery. The airways would seem to act as a template for pulmonary artery development. This study provides a framework for studying the signaling mechanisms controlling the various aspects of lung development.
PMID 10919986
http://ajrccm.atsjournals.org/content/175/10/978.long
1999
Development of the innervation and airway smooth muscle in human fetal lung
Am J Respir Cell Mol Biol. 1999 Apr;20(4):550-60.
Sparrow MP, Weichselbaum M, McCray PB.
Department of Physiology, University of Western Australia, Nedlands, Australia. msparrow@cyllene.uwa.edu.au Abstract Human and porcine fetal airways have been shown to contract spontaneously from the first trimester, the latter also contracting in response to neural stimulation. Our object was to map immunohistochemically the innervation and its relationship to the airway smooth muscle (ASM) in the human fetal lung from early gestation to the postnatal period. Whole mounts of the bronchial tree were stained with antibodies to the pan-neuronal marker protein gene product 9.5, the Schwann cell marker S-100, and the ASM contractile protein alpha-actin, and imaged using confocal microscopy. By the end of the embryonic period (53 d gestation), the branching epithelial tubules in the primordial lung were covered with ASM to the base of the terminal sacs. An extensive plexus of nerve trunks containing nerve bundles, forming ganglia, and Schwann cells ensheathed the ASM. By 16 wk (canalicular stage), maturation of the innervation was advanced with two major nerve trunks running the length of the bronchial tree, giving rise to varicosed fibers lying on the ASM. An extensive nerve plexus in the mucosa was also present. The distal airways of infants who had died of Sudden Infant Death Syndrome were also covered with smooth muscle and were well innervated. Thus, an essentially complete coat of ASM and an abundant neural plexus ensheathing the airways are an integral part of the branching epithelial tubules from early in lung development.
PMID: 10100986
