Talk:2009 Lecture 10

Background Reading

• Transcriptional control of lung morphogenesis. Maeda Y, Davé V, Whitsett JA. Physiol Rev. 2007 Jan;87(1):219-44. Review. PMID: 17237346 Physiol Rev. - Good teaching diagrams

"The vertebrate lung consists of multiple cell types that are derived primarily from endodermal and mesodermal compartments of the early embryo. The process of pulmonary organogenesis requires the generation of precise signaling centers that are linked to transcriptional programs that, in turn, regulate cell numbers, differentiation, and behavior, as branching morphogenesis and alveolarization proceed. This review summarizes knowledge regarding the expression and proposed roles of transcription factors influencing lung formation and function with particular focus on knowledge derived from the study of the mouse. A group of transcription factors active in the endodermally derived cells of the developing lung tubules, including thyroid transcription factor-1 (TTF-1), beta-catenin, Forkhead orthologs (FOX), GATA, SOX, and ETS family members are required for normal lung morphogenesis and function. In contrast, a group of distinct proteins, including FOXF1, POD1, GLI, and HOX family members, play important roles in the developing lung mesenchyme, from which pulmonary vessels and bronchial smooth muscle develop. Lung formation is dependent on reciprocal signaling among cells of both endodermal and mesenchymal compartments that instruct transcriptional processes mediating lung formation and adaptation to breathing after birth."

• Regulation of early lung morphogenesis: questions, facts and controversies. Cardoso WV, Lü J. Development. 2006 May;133(9):1611-24. Review. PMID: 16613830

"During early respiratory system development, the foregut endoderm gives rise to the tracheal and lung cell progenitors. Through branching morphogenesis, and in coordination with vascular development, a tree-like structure of epithelial tubules forms and differentiates to produce the airways and alveoli. Recent studies have implicated the fibroblast growth factor, sonic hedgehog, bone morphogenetic protein, retinoic acid and Wnt signaling pathways, and various transcription factors in regulating the initial stages of lung development. However, the precise roles of these molecules and how they interact in the developing lung is subject to debate. Here, we review early stages in lung development and highlight questions and controversies regarding their molecular regulation."

• Development of the pulmonary veins; with reference to the embryology of anomalies of pulmonary venous return. NEILL CA. Pediatrics. 1956 Dec;18(6):880-7. No abstract available. PMID: 13378917 | Pediatrics

• Classic imaging signs of congenital cardiovascular abnormalities.

Ferguson EC, Krishnamurthy R, Oldham SA. Radiographics. 2007 Sep-Oct;27(5):1323-34. Review. PMID: 17848694 http://radiographics.rsna.org/content/27/5/1323.long

pulmonary vein origin

• Development and structures of the venous pole of the heart. Anderson RH, Brown NA, Moorman AF. Dev Dyn. 2006 Jan;235(1):2-9. Review. PMID: 16193508

"The origin of the pulmonary vein remains controversial. Although all now agree that the vein itself canalizes from a mid-pharyngeal strand at approximately 6 weeks of development in the human (Blom et al., [2001]) and opens into the atrium between the ridges marking the site of the dorsal mesocardial connection, arguments continue as to whether or not this part of the developing atrium should be considered part of the sinus venosus (Hochstetter, [1908]; Auër, [1941]). Some argue that the area should be considered as part of the sinus venosus because the tissues surrounding the dorsal mesocardium, along with those surrounding the systemic venous tributaries, stain positively for an antibody to human natural killer cells (deRuiter et al., [1995]). The staining properties of the antibody to the human killer cells, however, are also cited as evidence that cells are derived from the neural crest (Verberne et al., [1998]) or that they are primordia of conducting tissues (Blom et al., [1999]). In reality, these antibodies stain migrating populations of cells (Tucker et al., [1984]; Kuratani and Kirby, [1991]), including those derived from the neural crest, and those entering the heart to form the mediastinal myocardium. The neural crest, furthermore, also produces the parasympathetic neural input to the heart, which also enters the heart primarily through the venous pole. Positive staining of antibodies to human natural killer cells, therefore, does not prove that the myocardium surrounding the pulmonary vein is derived from the sinus venosus. In fact, our own findings using molecular markers show that the myocardium surrounding the pulmonary venous orifice, from the time of its first appearance within the developing atrium, stains positively for connexin40. Thus, it is readily distinguished from the primary myocardium surrounding the orifices of the systemic venous tributaries. This evidence, coupled with the timing of appearance of the pulmonary venous channel, at approximately Carnegie stage 12 in the human and during the ninth day in the mouse, shows that the pulmonary vein is a new structure. It does not take its origin from the sinus venosus, the latter never existing as a discrete compartment of the developing mammalian heart."

"The pulmonary vein, therefore, has never been part of the so-called sinus venosus, nor does it take its origin from the systemic venous tributaries."

human heart

• pulmonary vein opens initially as a solitary orifice adjacent to the atrioventricular junctions
• subsequent to the division of the primary atrial chamber into its right and left parts by growth of the primary atrial septum, the pulmonary veins remodel so as to gain separate entrances at the four corners of the roof of the body of the left atrium
• as the right pulmonary veins gain their entrance to the atrial roof infolding of the wall between their mouths and the orifices of the systemic venous sinus entering the right atrium.
• infolding produces the septum secundum (superior interatrial fold).

http://www.ncbi.nlm.nih.gov/pubmed/18456075

"Rapid clearance of fetal lung fluid is a key part of these changes, and is mediated in large part by transepithelial sodium reabsorption through amiloride-sensitive sodium channels in the alveolar epithelial cells, with only a limited contribution from mechanical factors and Starling forces. "

Embryological origin of airway smooth muscle. Badri KR, Zhou Y, Schuger L. Proc Am Thorac Soc. 2008 Jan 1;5(1):4-10. Review. PMID: 18094078

"Airway smooth muscle (SM) develops from local mesenchymal cells located around the tips of growing epithelial buds. These cells gradually displace from distal to proximal position alongside the bronchial tree, elongate, and begin to synthesize SM-specific proteins. Mechanical tension (either generated by cell spreading/elongation or stretch), as well as epithelial paracrine factors, regulates the process of bronchial myogenesis. The specific roles of many of these paracrine factors during normal lung development are currently unknown. It is also unknown how and if mechanical and paracrine signals integrate into a common myogenic pathway. Furthermore, as with vascular SM and other types of visceral SM, we are just beginning to elucidate the intracellular signaling pathways and the genetic program that controls lung myogenesis. Here we present what we have learned so far about the embryogenesis of bronchial muscle."

• Origin, differentiation, and maturation of human pulmonary veins. Hall SM, Hislop AA, Haworth SG. Am J Respir Cell Mol Biol. 2002 Mar;26(3):333-40. PMID: 11867341

"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."

http://www3.interscience.wiley.com/journal/122523254/abstract?CRETRY=1&SRETRY=0