No abstract

Mammalian forebrain development requires extensive cell migration for cells to reach their appropriate location in the adult brain. Defects in this migration result in human malformations and neurologic deficits. Thus, understanding the mechanisms underlying normal cell migration during development is essential to understanding the pathogenesis of human malformations. Radial glia are known to support radial cell migration, while axons have been proposed as substrate for some non-radially migrating cells. Herein we have directly tested the hypothesis that axons can support non-radial cell migration. One population of cells known to migrate non-radially is the inhibitory interneurons that move from the ganglionic eminence to the cerebral cortex. We first show that early born GABAergic cells colocalize with TAG-1-positive (TAG-1+) axons, while later born cells colocalize with intermediate weight neurofilament-positive, TAG-1-negative (TAG-1-) processes, suggesting temporal differences in substrate specificities. We next developed an in vitro assay that allows us to observe cell migration on axons in culture. Using this assay we find that early born medial ganglionic eminence-derived interneurons migrate preferentially on TAG-1+ axons, while later born cells only migrate on neurofilament-positive/TAG-1- processes. These data provide the first direct evidence that ganglionic eminence cells migrate on axons and that there is an age-dependent substrate preference. Furthermore, the assay developed and characterized herein provides a robust method to further study the molecular substrates and guidance cues of axonophilic cell migration in neural development.

No abstract

Malignant peripheral nerve sheath tumors are rare spindle-cell sarcomas derived from Schwann cells or pluripotent cells of the neural crest. They arise from the spinal roots, peripheral nerves, brachial and lumbosacral plexi, cranial nerves and terminal nerve fibers within soft tissue, intestine, lung and bone. These tumors recur either locally, or metastasize distally. Most of these tumors occur in association with neurofibromatosis type 1. Spinal cord metastasis from malignant nerve sheath tumors associated with neurofibromatosis type 1 is very rare. We describe a rare case of near-total spinal cord metastasis in a patient with malignant nerve sheath tumor in the absence of neurofibromatosis, and highlight the microscopic findings and natural history of this disease process.

A 5-year-old boy presented with mild autism and attention-deficit hyperactivity disorder (ADHD). Chromosomal microarray demonstrated a 1.7 Mb deletion at Xp22.31, which was consistent with X-linked ichthyosis (XLI). Further exam revealed dry, scaly skin on his abdomen and pretibial areas. Patients with mutations involving solely the STS gene or the recurrent ~2 Mb deletion may present with ADHD, whereas those with larger deletions including the NLGN4 gene can present with both ADHD and autism. However, our patient presented with mild autism in addition to ADHD despite having only the recurrent deletion without loss of NLGN4. Such neurological manifestations of XLI warrant attention as practical targets of clinical management.