https://www.cell.com/cell/pdf/S0092-8674(00)81812-7.pdf

Isolation of Angiopoietin-1, a Ligand for the TIE2 Receptor, by Secretion-Trap Expression Cloning

Vertebrates constantly remodel bone. The resorption of preexisting bone by osteoclasts and the formation of new bone by osteoblasts is strictly coordinated to maintain bone mass within defined limits. A few molecular determinants of bone remodelling that affect osteoclast activity have been characterized, but the molecular determinants of osteoblast activity are unknown. To investigate the role of osteocalcin, the most abundant osteoblast-specific non-collagenous protein, we have generated osteocalcin-deficient mice. These mice develop a phenotype marked by higher bone mass and bones of improved functional quality. Histomorphometric studies done before and after ovariectomy showed that the absence of osteocalcin leads to an increase in bone formation without impairing bone resorption. To our knowledge, this study provides the first evidence that osteocalcin is a determinant of bone formation.

/pdf/increased-bone-formation-in-osteocalcin-deficient-mice-57yx1bi33s.pdf

Increased bone formation in osteocalcin-deficient mice

Stem cells persist throughout life by self-renewing in numerous tissues including the central and peripheral nervous systems. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to progressive postnatal growth retardation and neurological defects. Here we show that Bmi-1 is required for the self-renewal of stem cells in the peripheral and central nervous systems but not for their survival or differentiation. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation. p16Ink4a deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem cells. This conserved requirement for Bmi-1 to promote self-renewal and to repress p16Ink4a expression suggests that a common mechanism regulates the self-renewal and postnatal persistence of diverse types of stem cell. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues.

Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation

http://www.lemkelab.org/files/PDFsTAMPublications/Rothlin_et_al_Cell2007.pdf

TAM receptors are pleiotropic inhibitors of the innate immune response.

Malignant disease occurs when neoplastic cells abandon their primary site of accretion, cross tissue boundaries and penetrate the vasculature to colonize distant sites. This process --metastasis--is the aberrant counterpart of a physiological programme for organ regeneration and maintenance. Scatter factors and semaphorins, together with their receptors, help to orchestrate this programme. What are the differences between physiological and pathological activation of these signalling molecules, and can we exploit them therapeutically to prevent metastasis?

Greg Conn

Papers

The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases

Hepatocyte growth factor promotes motor neuron survival and synergizes with ciliary neurotrophic factor.