Contractile activity of skeletal musculature involved in breathing is essential for normal lung cell differentiation, as revealed in <i>Myf5−/−:MyoD−/−</i> embryos

Inanlou, Mohammad Reza; Kablar, Boris

doi:10.1002/dvdy.20381

Cited by 26 publications

(20 citation statements)

References 91 publications

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“…For example, it has been shown that normal lung development requires spontaneous fetal breathing movements in humans and mice [66], [67], [68]. In humans developmental defects caused by fetal akinesia include multiple pterygium syndrome (OMIM #265000 and #253290) and the fetal akinesia deformation sequence (FADS; OMIM #208150).…”

Section: Discussionmentioning

confidence: 99%

Cleft Palate Is Caused by CNS Dysfunction in Gad1 and Viaat Knockout Mice

Westmoreland

Summers

et al. 2010

PLoS ONE

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BackgroundPrevious studies have shown that disruption of GABA signaling in mice via mutations in the Gad1, Gabrb3 or Viaat genes leads to the development of non-neural developmental defects such as cleft palate. Studies of the Gabrb3 and Gad1 mutant mice have suggested that GABA function could be required either in the central nervous system or in the palate itself for normal palatogenesis.Methodology/Principal FindingsTo further examine the role of GABA signaling in palatogenesis we used three independent experimental approaches to test whether Gad1 or Viaat function is required in the fetal CNS for normal palate development. We used oral explant cultures to demonstrate that the Gad1 and Viaat mutant palates were able to undergo palatogenesis in culture, suggesting that there is no defect in the palate tissue itself in these mice. In a second series of experiments we found that the GABAA receptor agonist muscimol could rescue the cleft palate phenotype in Gad1 and Viaat mutant embryos. This suggested that normal multimeric GABAA receptors in the CNS were necessary for normal palatogenesis. In addition, we showed that CNS-specific inactivation of Gad1 was sufficient to disrupt palate development.Conclusions/SignificanceOur results are consistent with a role for Gad1 and Viaat in the central nervous system for normal development of the palate. We suggest that the alterations in GABA signaling lead to non-neural defects such as cleft palate as a secondary effect due to alterations in or elimination of fetal movements.

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Section: Discussionmentioning

confidence: 99%

Cleft Palate Is Caused by CNS Dysfunction in Gad1 and Viaat Knockout Mice

Westmoreland

Summers

et al. 2010

PLoS ONE

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“…In the absence of skeletal and/or diaphragm muscles, embryos lack fetal breathing movements, which causes reduced lung size, reduced sacculation and lung patterning defects (Ackerman et al, 2005;Inanlou and Kablar, 2003;Inanlou and Kablar, 2005a;Inanlou and Kablar, 2005b). Similarly, muscles cannot contract in Musk mutants due to the absence of NMJs, and these embryos display pulmonary hypoplasia (DeChiara et al, 1996).…”

Section: Lrp4 Is Required For Formation Of the Nmjmentioning

confidence: 97%

LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction

2006

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Low-density lipoprotein receptor-related protein 4 (Lrp4) is a member of a family of structurally related, single-pass transmembrane proteins that carry out a variety of functions in development and physiology, including signal transduction and receptor-mediated endocytosis. Lrp4 is expressed in multiple tissues in the mouse, and is important for the proper development and morphogenesis of limbs, ectodermal organs, lungs and kidneys. We show that Lrp4 is also expressed in the post-synaptic endplate region of muscles and is required to form neuromuscular synapses. Lrp4-mutant mice die at birth with defects in both presynaptic and postsynaptic differentiation, including aberrant motor axon growth and branching, a lack of acetylcholine receptor and postsynaptic protein clustering, and a failure to express postsynaptic genes selectively by myofiber synaptic nuclei. Our data show that Lrp4 is required during the earliest events in postsynaptic neuromuscular junction (NMJ) formation and suggest that it acts in the early, nerveindependent steps of NMJ assembly. The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes.

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“…Cyclic mechanical distension, without creep, is important in aiding the differentiation of type I pneumocytes [Gutierrez et al, 1998;Dobbs and Gutierrez, 2001] and the final differentiation of type II pneumocytes [Inanlou and Kablar, 2005b]. During fetal development, fetal breathing movements are important for the advanced development of pulmonary tissue [Inanlou and Kablar, 2005a].…”

Section: Discussionmentioning

confidence: 99%

Matrix Composition and Mechanics of Decellularized Lung Scaffolds

Petersen

Calle²,

Colehour³

et al. 2011

Cells Tissues Organs

209

185

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The utility of decellularized native tissues for tissue engineering has been widely demonstrated. Here, we examine the production of decellularized lung scaffolds from native rodent lung using two different techniques, principally defined by use of either the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) or sodium dodecyl sulfate (SDS). All viable cellular material is removed, including at least 99% of DNA. Histochemical staining and mechanical testing indicate that collagen and elastin are retained in the decellularized matrices with CHAPS-based decellularization, while SDS-based decellularization leads to loss of collagen and decline in mechanical strength. Quantitative assays confirm that most collagen is retained with CHAPS treatment but that about 80% of collagen is lost with SDS treatment. In contrast, for both detergent methods, at least 60% of elastin content is lost along with about 95% of native proteoglycan content. Mechanical testing of the decellularized scaffolds indicates that they are mechanically similar to native lung using CHAPS decellularization, including retained tensile strength and elastic behavior, demonstrating the importance of collagen and elastin in lung mechanics. With SDS decellularization, the mechanical integrity of scaffolds is significantly diminished with some loss of elastic function as well. Finally, a simple theoretical model of peripheral lung matrix mechanics is consonant with our experimental findings. This work demonstrates the feasibility of producing a decellularized lung scaffold that can be used to study lung matrix biology and mechanics, independent of the effects of cellular components.

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Contractile activity of skeletal musculature involved in breathing is essential for normal lung cell differentiation, as revealed in Myf5−/−:MyoD−/− embryos

Cited by 26 publications

References 91 publications

Cleft Palate Is Caused by CNS Dysfunction in Gad1 and Viaat Knockout Mice

Cleft Palate Is Caused by CNS Dysfunction in Gad1 and Viaat Knockout Mice

LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction

Matrix Composition and Mechanics of Decellularized Lung Scaffolds

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