Leptin reverses the inhibitory effect of caloric restriction on longitudinal growth.
AuthorsGat-Yablonski G, Ben-Ari T, Shtaif B, Potievsky O, Moran O, Eshet R, Maor G, Segev Y, Phillip M
JournalEndocrinology
PubMed ID14525912
'Caloric imbalance, particularly in critical periods of growth and development, is often the underlying cause of growth abnormalities. Serum levels of leptin are elevated in obesity and are low in malnutrition and malabsorption. The aim of the present study was to determine whether leptin integrates energy levels and growth in ... More
Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa.
AuthorsAkiyama H, Chaboissier MC, Behringer RR, Rowitch DH, Schedl A, Epstein JA, de Crombrugghe B,
JournalProc Natl Acad Sci U S A
PubMed ID15096597
'Epithelial-mesenchymal transformation is a critical developmental process reiterated in multiple organs throughout embryogenesis. Formation of endocardial cushions, primordia of valves and septa, is a classic example of epithelial-mesenchymal transformation. Several gene mutations are known to affect cardiac valve formation. Sox9 is activated when endocardial endothelial cells undergo mesenchymal transformation and ... More
Chondrocytic Atf4 regulates osteoblast differentiation and function via Ihh.
AuthorsWang W, Lian N, Ma Y, Li L, Gallant RC, Elefteriou F, Yang X
JournalDevelopment
PubMed ID22190639
'Atf4 is a leucine zipper-containing transcription factor that activates osteocalcin (Ocn) in osteoblasts and indian hedgehog (Ihh) in chondrocytes. The relative contribution of Atf4 in chondrocytes and osteoblasts to the regulation of skeletal development and bone formation is poorly understood. Investigations of the Atf4(-/-);Col2a1-Atf4 mouse model, in which Atf4 is ... More
The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6.
AuthorsAkiyama H, Chaboissier MC, Martin JF, Schedl A, de Crombrugghe B,
JournalGenes Dev
PubMed ID12414734
'To examine whether the transcription factor Sox9 has an essential role during the sequential steps of chondrocyte differentiation, we have used the Cre/loxP recombination system to generate mouse embryos in which either Sox9 is missing from undifferentiated mesenchymal cells of limb buds or the Sox9 gene is inactivated after chondrogenic ... More
Deletion of laminin-8 results in increased tumor neovascularization and metastasis in mice.
AuthorsZhou Z, Doi M, Wang J, Cao R, Liu B, Chan KM, Kortesmaa J, Sorokin L, Cao Y, Tryggvason K
JournalCancer Res
PubMed ID15205311
'Laminin-8 (alpha 4 beta 1 gamma 1) is one of the major laminin isoforms expressed in vascular endothelial basement membranes. Here we show that deletion of laminin-8 in mice affects angiogenesis under pathological conditions. Murine tumor models used in laminin alpha 4-deficient mice results in hyperneovascularization and significant promotion of ... More
Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy.
AuthorsMayhew CN, Bosco EE, Fox SR, Okaya T, Tarapore P, Schwemberger SJ, Babcock GF, Lentsch AB, Fukasawa K, Knudsen ES
JournalCancer Res
PubMed ID15930274
'The liver exhibits an exquisitely controlled cell cycle, wherein hepatocytes are maintained in quiescence until stimulated to proliferate. The retinoblastoma tumor suppressor, pRB, plays a central role in proliferative control by inhibiting inappropriate cell cycle entry. In many cases, liver cancer arises due to aberrant cycles of proliferation, and correspondingly, ... More
Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction.
AuthorsPlaks V, Rinkenberger J, Dai J, Flannery M, Sund M, Kanasaki K, Ni W, Kalluri R, Werb Z,
Journal
PubMed ID23776237
The pregnancy complication preeclampsia (PE), which occurs in approximately 3% to 8% of human pregnancies, is characterized by placental pathologies that can lead to significant fetal and maternal morbidity and mortality. Currently, the only known cure is delivery of the placenta. As the etiology of PE remains unknown, it is ... More
Interactions between Sox9 and beta-catenin control chondrocyte differentiation.
AuthorsAkiyama H, Lyons JP, Mori-Akiyama Y, Yang X, Zhang R, Zhang Z, Deng JM, Taketo MM, Nakamura T, Behringer RR, McCrea PD, de Crombrugghe B,
JournalGenes Dev
PubMed ID15132997
Chondrogenesis is a multistep process that is essential for endochondral bone formation. Previous results have indicated a role for beta-catenin and Wnt signaling in this pathway. Here we show the existence of physical and functional interactions between beta-catenin and Sox9, a transcription factor that is required in successive steps of ... More
Conditional expression of fibroblast growth factor-7 in the developing and mature lung.
AuthorsTichelaar JW, Lu W, Whitsett JA,
JournalJ Biol Chem
PubMed ID10766812
Effects of fibroblast growth factor-7 (FGF-7) on lung morphogenesis, respiratory epithelial cell differentiation, and proliferation were assessed in transgenic mice in which the human FGF-7 cDNA was controlled by a conditional promoter under the direction of regulatory elements from either the human surfactant protein-C (SP-C) or rat Clara cell secretory ... More
Cerebellar deficits and hyperactivity in mice lacking Smad4.
AuthorsZhou YX, Zhao M, Li D, Shimazu K, Sakata K, Deng CX, Lu B
JournalJ Biol Chem
PubMed ID12896967
Smad4 is a central mediator of TGF-beta signals, which are known to play essential roles in many biological processes. Using a Cre-loxP approach to overcome early embryonic lethality, we have studied functions of TGF-beta/Smad4 signals in the central nervous system (CNS). No obvious deficits were detected in mice carrying the ... More
Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation.
AuthorsBraren R, Hu H, Kim YH, Beggs HE, Reichardt LF, Wang R
JournalJ Cell Biol
PubMed ID16391003
Morphogenesis of a vascular network requires dynamic vessel growth and regression. To investigate the cellular mechanism underlying this process, we deleted focal adhesion kinase (FAK), a key signaling mediator, in endothelial cells (ECs) using Tie2-Cre mice. Targeted FAK depletion occurred efficiently early in development, where mutants exhibited a distinctive and ... More
Protein tyrosine phosphatase-like A regulates myoblast proliferation and differentiation through MyoG and the cell cycling signaling pathway.
AuthorsLin X, Yang X, Li Q, Ma Y, Cui S, He D, Lin X, Schwartz RJ, Chang J
JournalMol Cell Biol
PubMed ID22106411
Protein tyrosine phosphatase-like A (PTPLa) has been implicated in skeletal myogenesis and cardiogenesis. Mutations in PTPLa correlated with arrhythmogenic right ventricular dysplasia in humans and congenital centronuclear myopathy with severe hypotonia in dogs. The molecular mechanisms of PTPLa in myogenesis are unknown. In this report, we demonstrate that PTPLa is ... More