Expression of beta-nerve growth factor receptor mRNA in Sertoli cells downregulated by testosterone

Nerve growth factor (NGF) is synthesized in male germ cells. The NGF receptor (NGFR) mRNA was found in the Sertoli cells of rat testis. Hypophysectomy increased both NGFR mRNA in testis and the number of NGFR hybridizing cells in seminiferous tubules. This was suppressed by treatment with chorionic gonadotropin or testosterone, but not with follicle-stimulating hormone. The NGFR mRNA also increased after destruction of Leydig cells or blocking of the androgen receptor. This suggests that NGF produced by male germ cells regulates testicular function in an androgen-modulated fashion by mediating an interaction germ and Sertoli cells.     

Electrophoretic separations of large DNA molecules by periodic inversion of the electric field

In gel electrophoresis, nucleic acids and protein-detergent complexes larger than a threshold size all migrate at the same rate. For DNA molecules, this effect can be overcome by the simple procedure of periodically inverting the electric field. Tuning the frequency of the field inversions from 10 to 0.01 hertz, makes it possible to resolve selectively DNA's in the size range 15 to greater than 700 kilobase pairs.     

A chromosome 21 critical region does not cause specific Down syndrome phenotypes

The "Down syndrome critical region" (DSCR) is a chromosome 21 segment purported to contain genes responsible for many features of Down syndrome (DS), including craniofacial dysmorphology. We used chromosome engineering to create mice that were trisomic or monosomic for only the mouse chromosome segment orthologous to the DSCR and assessed dysmorphologies of the craniofacial skeleton that show direct parallels with DS in mice with a larger segmental trisomy. The DSCR genes were not sufficient and were largely not necessary to produce the facial phenotype. These results refute specific predictions of the prevailing hypothesis of gene action in DS.     

Medulloblastoma growth inhibition by hedgehog pathway blockade

Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.     

Control of stress-dependent cardiac growth and gene expression by a microRNA

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of alpha-myosin heavy chain (alphaMHC) and up-regulation of betaMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism. Thus, the alphaMHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.