Endocranial features of Australopithecus africanus revealed by 2- and 3-D computed tomography

The earliest hominid from South Africa, Australopithecus africanus, is known from only six specimens in which accurate assessment of endocranial capacity and cranial venous outflow pattern can be obtained. This places a severe limit on a number of hypotheses concerning early hominid evolution, particularly those involving brain-body size relationships and adaptations of the circulatory system to evolving upright posture. Advances in high-resolution two- and three-dimensional computed tomography (CT) now allow the inclusion of another important specimen to this list, MLD 37/38 from Makapansgat. A new computer imaging technique is described that "reconstructs" the missing portions of the endocranial cavity in order to determine endocranial capacity. In addition, CT evaluation allows assessment of cranial venous outflow pattern even in cases where the endocranial cavity is completely filled with stone matrix. Results show that endocranial capacity in this specimen is less than originally proposed and also support the view that gracile and robust australopithecines evolved different cranial venous outflow patterns in response to upright postures.     

Axonal neuregulin-1 regulates myelin sheath thickness

In the nervous system of vertebrates, myelination is essential for rapid and accurate impulse conduction. Myelin thickness depends on axon fiber size. We use mutant and transgenic mouse lines to show that axonal Neuregulin-1 (Nrg1) signals information about axon size to Schwann cells. Reduced Nrg1 expression causes hypomyelination and reduced nerve conduction velocity. Neuronal overexpression of Nrg1 induces hypermyelination and demonstrates that Nrg1 type III is the responsible isoform. We suggest a model by which myelin-forming Schwann cells integrate axonal Nrg1 signals as a biochemical measure of axon size.     

Control of crystal size and lattice formation by starmaker in otolith biomineralization

The stone-like otoliths from the ears of teleost fishes are involved in balance and hearing and consist of calcium carbonate crystallites embedded in a protein framework. We report that a previously unknown gene, starmaker, is required in zebrafish for otolith morphogenesis. Reduction of starmaker activity by injection of modified antisense oligonucleotides causes a change in the crystal lattice structure and thus a change in otolith morphology. The expression pattern of starmaker, along with the presence of the protein on the growing otolith, suggest that the expression levels of starmaker control the shape of the otoliths.     

Dynamic visualization of thrombopoiesis within bone marrow

Platelets are generated from megakaryocytes (MKs) in mammalian bone marrow (BM) by mechanisms that remain poorly understood. Here we describe the use of multiphoton intravital microscopy in intact BM to visualize platelet generation in mice. MKs were observed as sessile cells that extended dynamic proplatelet-like protrusions into microvessels. These intravascular extensions appeared to be sheared from their transendothelial stems by flowing blood, resulting in the appearance of proplatelets in peripheral blood. In vitro, proplatelet production from differentiating MKs was enhanced by fluid shear. These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow-induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis.     

Kinetics of morphogen gradient formation

In the developing fly wing, secreted morphogens such as Decapentaplegic (Dpp) and Wingless (Wg) form gradients of concentration providing positional information. Dpp forms a longer-range gradient than Wg. To understand how the range is controlled, we measured the four key kinetic parameters governing morphogen spreading: the production rate, the effective diffusion coefficient, the degradation rate, and the immobile fraction. The four parameters had different values for Dpp versus Wg. In addition, Dynamin-dependent endocytosis was required for spreading of Dpp, but not Wg. Thus, the cellular mechanisms of Dpp and Wingless spreading are different: Dpp spreading requires endocytic, intracellular trafficking.