Abstract:
:Alveologenesis is the final step of lung maturation, which subdivides the alveolar region of the lung into smaller units called alveoli. Each of the nascent dividers serves as a new gas-exchange surface, and collectively they drastically increase the surface area for breathing. Disruption of alveologenesis results in simplification of alveoli, as is seen in premature infants diagnosed with bronchopulmonary dysplasia (BPD), a prevalent lung disease that is often associated with lifelong breathing deficiencies. To date, a majority of studies of alveologenesis rely on two-dimensional (2D) analysis of tissue sections. Given that an overarching theme of alveologenesis is thinning and extension of the epithelium and mesenchyme to facilitate gas exchange, often only a small portion of a cell or a cellular structure is represented in a single 2D plane. Here, we use a three-dimensional (3D) approach to examine the structural architecture and cellular composition of myofibroblasts, alveolar type 2 cells, elastin and lipid droplets in normal as well as BPD-like mouse lung. We found that 2D finger-like septal crests, commonly used to depict growing alveolar septae, are often artifacts of sectioning through fully established alveolar walls. Instead, a more accurate representation of growing septae are 3D ridges that are lined by platelet-derived growth factor receptor alpha (PDGFRA) and alpha smooth muscle actin (α-SMA)-expressing myofibroblasts, as well as the elastin fibers that they produce. Accordingly in 3D, both α-SMA and elastin were each found in connected networks underlying the 3D septal ridges rather than as isolated dots at the tip of 2D septal crests. Analysis through representative stages of alveologenesis revealed unappreciated dynamic changes in these patterns. PDGFRA-expressing cells are only α-SMA-positive during the first phase of alveologenesis, but not in the second phase, suggesting that the two phases of septae formation may be driven by distinct mechanisms. Thin elastin fibers are already present in the alveolar region prior to alveologenesis, suggesting that during alveologenesis, there is not only new elastin deposition, but also extensive remodeling to transform thin and uniformly distributed fibers into thick cables that rim the nascent septae. Analysis of several genetic as well as hyperoxia-induced models of BPD revealed that the myofibroblast organization is perturbed in all, regardless of whether the origin of defect is epithelial, mesenchymal, endothelial or environmental. Finally, analysis of relative position of PDGFRA-positive cells and alveolar type 2 cells reveal that during alveologenesis, these two cell types are not always adjacent to one another. This result suggests that the niche and progenitor relationship afforded by their close juxtaposition in the adult lung may be a later acquired property. These insights revealed by 3D reconstruction of the septae set the foundation for future investigations of the mechanisms driving normal alveologenesis, as well as causes of alveolar simplification in BPD.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Branchfield K,Li R,Lungova V,Verheyden JM,McCulley D,Sun Xdoi
10.1016/j.ydbio.2015.11.017subject
Has Abstractpub_date
2016-01-15 00:00:00pages
429-41issue
2eissn
0012-1606issn
1095-564Xpii
S0012-1606(15)30307-9journal_volume
409pub_type
杂志文章abstract::The sizes of amino acid pools in growing Xenopus laevis oocytes have been measured. The total free amino acid content per oocyte increases nearly 25-fold during oocyte growth. Together, glutamic acid and aspartic acid account for approximately 59-75% of the total amino acid pool in Xenopus oocytes. On the other hand, ...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(87)90480-5
更新日期:1987-11-01 00:00:00
abstract::During early development, GATA factors have been shown to be important for key events of coronary vasculogenesis, including formation of the epicardium. Myocardial GATA factors are required for coronary vascular (CV) formation; however, the role of epicardial localized GATAs in this process has not been addressed. The...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2013.12.033
更新日期:2014-02-01 00:00:00
abstract::Vertebrate pigment cells are derived from neural crest, a tissue that also forms most of the peripheral nervous system and a variety of ectomesenchymal cell types. Formation of pigment cells from multipotential neural crest cells involves a number of common developmental processes. Pigment cells must be specified; the...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.2000.9840
更新日期:2000-09-15 00:00:00
abstract::Electroporation-based assays were used to test whether the myogenic regulatory factor (MRF) of Ciona intestinalis (CiMRF) interferes with endogenous developmental programs, and to evaluate the importance of its unusual N-terminus for muscle development. We found that CiMRF suppresses both notochord and endoderm develo...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2018.10.010
更新日期:2019-04-15 00:00:00
abstract::To form a gonad, germ cells (GCs) and somatic gonadal precursor cells (SGPs) must migrate to the correct location in the developing embryo and establish the cell-cell interactions necessary to create proper gonad architecture. During gonad morphogenesis, SGPs send out cellular extensions to ensheath the individual GCs...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2012.04.027
更新日期:2012-07-15 00:00:00
abstract::Sonic hedgehog is a secreted factor regulating patterning of the anterior-posterior axis in the developing limb. The signaling pathway mediating the transduction of the signal is still poorly understood. In Drosophila several genes are known to act downstream of hedgehog, the fly homolog of Sonic hedgehog. An importan...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1996.0300
更新日期:1996-11-25 00:00:00
abstract::In embryos of Patella vulgata at the 32-cell stage, one of the four vegetally located macromeres makes contacts with overlying animal micromeres. As a result, this macromere (designated 3D) divides significantly later than the other macromeres and forms the mesodermal stem cell 4d. Shortly before and during this inter...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(89)90239-x
更新日期:1989-04-01 00:00:00
abstract::In previous studies we found that two glycoproteins of 220 and 180 kDa account for 80-90% of the material dissolved from the vitelline coat (VC) of Unio elongatulus egg (Focarelli and Rosati, 1993). The two glycoproteins were purified by electroelution and used to raise the corresponding polyclonal antibodies. Immunof...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1995.1308
更新日期:1995-10-01 00:00:00
abstract::Congenital diseases caused by abnormal development of the cranial neural crest usually present craniofacial malformations and heart defects while the precise mechanism is not fully understood. Here, we show that the zebrafish eif3ba mutant caused by pseudo-typed retrovirus insertion exhibited a similar phenotype due t...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2013.06.009
更新日期:2013-09-01 00:00:00
abstract::Reproductive plasticity is the ability of an animal to modulate its reproductive functions in response to environmental changes. For example, Caenorhabditis elegans, a free-living nematode, can adjust the onsets of oogenesis and embryogenesis under harsh environmental conditions, including starvation. However, the mol...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2017.08.014
更新日期:2017-10-01 00:00:00
abstract::The development of the vertebrate inner ear is a complex process that has been investigated in several model organisms. In this work, we examined genetic interactions regulating early development of otic structures in medaka. We demonstrate that misexpression of Fgf8, Dlx3b and Foxi1 during early gastrulation is suffi...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2007.04.022
更新日期:2007-07-15 00:00:00
abstract::Conjugation in Tetrahymena represents an ordered developmental pathway which represents the sexual phase of the ciliate life cycle. This pathway is initiated when starved cells of opposite mating types are mixed and are allowed to make a series of cell-cell contacts (a period termed costimulation) which lead to the fo...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(91)90075-e
更新日期:1991-02-01 00:00:00
abstract::The mouse prostate gland develops by branching morphogenesis from the urogenital epithelium and mesenchyme. Androgens and developmental factors, including FGF10 and SHH, promote prostate growth (Berman, D.M., Desai, N., Wang, X., Karhadkar, S.S., Reynon, M., Abate-Shen, C., Beachy, P.A., Shen, M.M., 2004. Roles for He...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2005.08.018
更新日期:2005-12-15 00:00:00
abstract::Ca2+-sensitive microelectrodes were used to study changes in cytoplasmic free calcium during progesterone-induced meiotic maturation in Xenopus laevis oocytes. In contrast to previous reports, no changes were detected during the maturation process, although a large activation pulse of Ca2+ was seen when in vitro matur...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(85)90475-0
更新日期:1985-06-01 00:00:00
abstract::The survival effects of brain-derived neurotrophic factor (BDNF) on the ganglion cells of the chick retina were studied in vitro at different embryonic ages. We found these effects to be strongly age-dependent: at E5, when the first ganglion cell axons have crossed the optic chiasm, but not yet reached the tectum, gan...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(89)90256-x
更新日期:1989-12-01 00:00:00
abstract::Fertilization overcomes meiotic arrest by triggering a series of biochemical events, resulting in activation of the egg. A small group of protein tyrosine kinases (PTKs) have been identified in eggs of invertebrates and lower vertebrates and inhibitor studies have suggested that they play a role in late events of egg ...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1997.8816
更新日期:1998-02-01 00:00:00
abstract::Transcription factors (TFs) can regulate different sets of genes to determine specific cell types by means of combinatorial codes. We previously identified closely-spaced TF binding motifs located 8.2-8.5 kb 5' to the ATG of the murine Pou4f3 gene, a gene required for late hair cell (HC) differentiation and survival. ...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2012.09.002
更新日期:2012-12-01 00:00:00
abstract::Mutations in the Bone Morphogenetic Protein (BMP) pathway are associated with a range of defects in skeletal formation. Genetic analysis of BMP signaling requirements is complicated by the presence of three partially redundant BMPs that are required for multiple stages of limb development. We generated an inducible al...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2014.07.003
更新日期:2014-09-15 00:00:00
abstract::In the embryonic mouse retina, retinoic acid (RA) is unevenly distributed along the dorsoventral axis: RA-rich zones in dorsal and ventral retina are separated by a horizontal RA-poor stripe that contains the RA-inactivating enzyme CYP26A1. To explore the developmental role of this arrangement, we studied formation of...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2004.08.032
更新日期:2004-12-01 00:00:00
abstract::Sequence analysis of cDNA clones encoding fibronectin (FN) from Xenopus laevis reveals extensive amino acid identities with other vertebrate FNs, including the presence of the Arg-Gly-Asp (RGD) cell attachment site in type III-10 and of a second, cell-binding site (EILDV) in the alternative spliced V region of the pro...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(92)90291-n
更新日期:1992-02-01 00:00:00
abstract::A newly defined genetic locus designated lethal (1) optic ganglion reduced (l(1)ogre: 1-18.8, 6E1/2-6E4/5) is characterized. Four alleles have been isolated, one organismal viable and three organismal lethals. Histological analyses of these mutants at the light microscopic level have detected defects only in the devel...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(85)90009-0
更新日期:1985-03-01 00:00:00
abstract::Cadherin-mediated cell-cell interactions are thought to be critical in controlling cell sorting during embryogenesis. Here, we report that chimeric embryos generated with N-cadherin-deficient (N-cadherin(-/-)) embryonic stem cells develop further than embryos completely lacking N-cadherin only when the myocardium cons...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.2001.0250
更新日期:2001-06-01 00:00:00
abstract::To analyse cell migration and the differentiation potential of migratory stem cells in Hydractinia, we generated animals with an eGFP reporter gene stably expressed and transmitted via the germline. The transgene was placed under the control of two different actin promoters and the promoter of elongation factor-1α. On...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2010.08.017
更新日期:2010-12-01 00:00:00
abstract::The morphology of skeletal tissues formed in each of the branchial arches of higher vertebrates is unique. In addition to these structures, which are derived from the neural crest, the crest-derived connective tissues and mesodermal muscles also form different patterns in each of the branchial arches. The objective of...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/0012-1606(83)90318-4
更新日期:1983-03-01 00:00:00
abstract::In the zebrafish embryo, cells fated to give rise to the rostral brain move in a concerted fashion and retain tissue coherence during morphogenesis. We demonstrate here that Otx proteins have a dramatic effect on cell-cell interactions when expressed ectopically in the zebrafish embryo. Injection of zebrafish Otx1 or ...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.2000.9771
更新日期:2000-07-15 00:00:00
abstract::John W. Saunders, Jr. made seminal discoveries unveiling how chick embryos develop their limbs. He discovered the apical ectodermal ridge (AER), the zone of polarizing activity (ZPA), and the domains of interdigital cell death within the developing limb and determined their function through experimental analysis. Thes...
journal_title:Developmental biology
pub_type: 杂志文章,评审
doi:10.1016/j.ydbio.2016.11.005
更新日期:2017-09-15 00:00:00
abstract::In the nematode Caenorhabditis elegans, the BMP-related growth factor DBL-1 regulates body size and male tail morphogenesis via a conserved receptor/Smad signaling pathway. Smads are transcription factors, but rely on transcription cofactors for appropriate regulation of target genes in response to TGF-beta- and BMP-r...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2007.02.038
更新日期:2007-05-15 00:00:00
abstract::The zebrafish fin is an excellent system to study the mechanisms of dermal bone patterning. Fin rays are segmented structures that form successive bifurcations both during ontogenesis and regeneration. Previous studies showed that sonic hedgehog (shha) may regulate regenerative bone patterning based on its expression ...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2012.03.008
更新日期:2012-05-15 00:00:00
abstract::The spermatid nucleus and cytoplasm undergo dramatic morphological modifications during spermatid differentiation into mature sperm. Some of the external force causing this nuclear shaping is generated by a microtubular structure termed the manchette, which attaches to the perinuclear ring of the spermatid. Here, we r...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.2001.0286
更新日期:2001-08-15 00:00:00
abstract::The homeobox gene sine oculis (so) is required for the development of the entire visual system in Drosophila, which includes the compound eyes, the ocelli, the optic lobe of the brain and the Bolwig's organ. During ocelli development, so expression labels, together with eyes absent (eya), the emergence of the ocellar ...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2010.05.494
更新日期:2010-08-15 00:00:00