A model of neocortical area patterning in the lissencephalic mouse may hold for larger gyrencephalic brains.

In the mouse, two telencephalic signaling centers orchestrate embryonic patterning of the cerebral cortex. From the rostral patterning center in the telencephalon, the Fibroblast Growth Factor, FGF8, disperses as a morphogen to establish the rostral to caudal axis of the neocortical area map. FGF8 coordinates with Wnt3a from the cortical hem to regulate graded expression of transcription factors that position neocortical areas, and control hippocampal development. Whether similar signaling centers pattern the much larger cortices of carnivore and primate species, however, is unclear. The limited dispersion range of FGF8 and Wnt3a is inconsistent with patterning larger cortical primordia. Yet the implication that different mechanisms organize cortex in different mammals flies in the face of the tenet that developmental patterning mechanisms are conserved across vertebrate species. In the present study, both signaling centers were identified in the ferret telencephalon, as were expression gradients of the patterning transcription factor genes regulated by FGF8 and Wnt3a. Notably, at the stage corresponding to the peak period of FGF8 signaling in the mouse neocortical primordium (NP), the NP was the same size in ferret and mouse, which would allow morphogen patterning of the ferret NP. Subsequently, the size of ferret neocortex shot past that of the mouse. Images from online databases further suggest that NP growth in humans, too, is slowed in early cortical development. We propose that if early growth in larger brains is held back, mechanisms that pattern the neocortical area map in the mouse could be conserved across mammalian species.

Intracranial ultrasound abnormalities and fetal cytomegalovirus infection: report of 8 cases and review of the literature.

OBJECTIVES: The aim of this study was to evaluate fetal intracranial and other ultrasonographic findings in cytomegalovirus (CMV) infection. METHODS: Data on amniotic fluid CMV-DNA-PCR-positive pregnancies detected in our institution between January 2006 and June 2009 were reviewed retrospectively. Fetal biometric measurements, fetal anatomy, amniotic fluid volume, placental thickness and texture were analyzed for abnormalities. RESULTS: Eight fetuses were diagnosed with congenital CMV infection during the study interval. Their mean gestational age at diagnosis was 25.8 weeks (range: 23-29). All fetuses had intracranial abnormalities; increased periventricular echogenicity (n = 7), ventriculomegaly (n = 5), intracranial calcifications (n = 4), intraventricular adhesions (n = 4), thalamic hyperechogenicity (n = 3), mega cisterna magna (n = 3), lissencephaly (n = 2), vermian defect (n = 2) and cerebellar cyst (n = 1). All of them had accompanying extracranial findings, including hyperechogenic bowel (n = 6), cardiomegaly (n = 3), pericardial effusion (n = 2) and hepatosplenomegaly (n = 1). Intrauterine growth retardation was detected in 3 cases. Five pregnancies were terminated, and 1 intrauterine death occurred. The remaining 2 delivered vaginally at term. One of the live-born babies suffers from tetraparesis, mental retardation and autism, and the other has mild hemiplegia. CONCLUSIONS: The spectrum of sonographic findings may vary widely in patients with congenital CMV infection in the prenatal period. CMV should be kept in mind in differential diagnosis, particularly in fetuses with intracranial sonographic findings such as ventriculomegaly, calcifications, intraventricular adhesions and increased periventricular echogenicity.

Genetic mechanisms underlying abnormal neuronal migration in classical lissencephaly.

Classical lissencephaly is a human developmental brain disorder characterized by a paucity of cortical gyration and thickening of the cortical gray matter, leading to severe epilepsy and mental retardation. Loss-of-function mutations in the microtubule-associated protein encoding genes, PAFAH1B1 (encoding the protein LIS1), DCX and TUBA1A have been implicated in the pathogenesis of the condition. Animal models are required to understand the basis of this disease, which is a challenge, given that mice normally have a smooth cortex. Recent advances toward this goal have come from stepwise reduction in gene function, deletion of redundant genes and acute gene inactivation using short hairpin RNA (shRNA). These approaches have implicated genes that regulate the microtubule cytoskeleton during neuronal division, migration and maturation.