Tyrosine phosphatase MEG2 modulates murine development and platelet and lymphocyte activation through secretory vesicle function.

MEG2, a protein tyrosine phosphatase with a unique NH2-terminal lipid-binding domain, binds to and is modulated by the polyphosphoinositides PI(4,5)P2 and PI(3,4,5)P3. Recent data implicate MEG2 in vesicle fusion events in leukocytes. Through the genesis of Meg2-deficient mice, we demonstrate that Meg2-/- embryos manifest hemorrhages, neural tube defects including exencephaly and meningomyeloceles, cerebral infarctions, abnormal bone development, and >90% late embryonic lethality. T lymphocytes and platelets isolated from recombination activating gene 2-/- mice transplanted with Meg2-/- embryonic liver-derived hematopoietic progenitor cells showed profound defects in activation that, in T lymphocytes, was attributable to impaired interleukin 2 secretion. Ultrastructural analysis of these lymphocytes revealed near complete absence of mature secretory vesicles. Taken together, these observations suggest that MEG2-mediated modulation of secretory vesicle genesis and function plays an essential role in neural tube, vascular, and bone development as well as activation of mature platelets and lymphocytes.

Ependymoblastomatous exencephaly: a unique fetal malformation.

Exencephaly/anencephaly is a rare neural tube defect occurring early in embryogenesis. We report a 14-week-old fetus with exencephaly in whom central nervous system tissue was developed and preserved. There were 2 symmetrical structures grossly resembling cerebral hemispheres, which on histologic and ultrastructural study, consisted of a combination of ependymoblastomatous rosettes and canals and primitive neural tissue. The brainstem and spinal cord were partially normally formed, although descending tracts were not apparent. No cerebellar tissue was found. The eyes were formed. This appears to represent a rare example of exencephaly not covered by skin, which did not undergo necrosis and early transformation into a residual area cerebrovasculosa, characteristic of anencephaly. It may be appropriate to regard this as a unique neural tube closure defect that might be termed "ependymoblastomatous exencephaly."

Ultrastructural study of the filum terminale and its elastic fibers.

OBJECTIVE: The filum terminale (FT) is a fibrovascular band involved in the pathophysiology of tethered cord syndrome (TCS). Its morphological and ultrastructural properties remain largely unknown even though they are thought to play a role in the generation of TCS in adult patients with normal level conus medullaris. MATERIALS AND METHODS: Twenty fresh adult human cadavers had their fila measured and removed. Transversal and longitudinal sections of the proximal, middle, and distal thirds of FT were submitted to light microscopy analysis with four different techniques. Five fila were selected for longitudinal and transversal scanning electron microscopy analysis. RESULTS: The bulk of the FT is composed of 5- to 20-microm thick longitudinal bundles of Type 1 collagen separated by 3- to 10-microm intervals, although capillaries and other elements may be present. A delicate (0.05-1.5 microm) meshwork of predominantly Type 3 collagen transversal fibers connects these bundles. Abundant longitudinally oriented elastic and elaunin fibers are found inside collagen bundles. A complex tridimensional structure is evidenced on electron microscopy. CONCLUSION: The longitudinal arrangement of collagen bundles and the impressive amount of elastic and elaunin fibers should elicit considerable elastic properties to the FT. An altered elasticity mechanism has been proposed for TCS; further studies are needed with TCS patients to define whether the collagen structure, Type 1/Type 3 proportion, or elastic fiber content are altered, which could lead to new histopathological definitions of TCS, helping neurosurgeons in the difficult management of TCS patients with normal level conus medullaris.

The Chiari II malformation: cause and impact.

INTRODUCTION: It is the Chiari II malformation and its effects that determine the quality of life of the individual born with spina bifida. DISCUSSION: The cause of this malformation has been a source of debate for many years. Understanding the cause enables strategies for the management of problems created by this malformation to be developed. An open neural tube defect allows fluid to escape from the cranial vesicles, altering the intracranial environment and leads to all of the brain changes seen in the Chiari II malformation. Decompression of the intracranial vesicles causes overcrowding, decrease in the size of the third ventricle, and changes in the fetal skull. It also permanently links the intracranial ventricular system to the spinal cord central canal.