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The cerebellum is the primary motor coordination center of the CNS and is also involved in cognitive processing and sensory discrimination. Multiple cerebellar malformations have been described in humans, however, their developmental and genetic etiologies currently remain largely unknown. In contrast, there is extensive literature describing cerebellar(More)
CASK is a multi-domain scaffolding protein that interacts with the transcription factor TBR1 and regulates expression of genes involved in cortical development such as RELN. Here we describe a previously unreported X-linked brain malformation syndrome caused by mutations of CASK. All five affected individuals with CASK mutations had congenital or postnatal(More)
The cerebellar rhombic lip and telencephalic cortical hem are dorsally located germinal zones which contribute substantially to neuronal diversity in the CNS, but the mechanisms that drive neurogenesis within these zones are ill defined. Using genetic fate mapping in wild-type and Lmx1a(-/-) mice, we demonstrate that Lmx1a is a critical regulator of(More)
Although human congenital cerebellar malformations are common, their molecular and developmental basis is still poorly understood. Recently, cilia-related gene deficiencies have been implicated in several congenital disorders that exhibit cerebellar abnormalities such as Joubert syndrome, Meckel-Gruber syndrome, Bardet-Biedl syndrome, and Orofaciodigital(More)
Allelic losses at 1p32-pter have been reported as frequent events in human non-small cell lung cancer (NSCLC). To further characterize the region of deletions, we studied loss of heterozygosity on a panel of 102 microdissected NSCLC samples with 20 polymorphic markers spanning 1p32-pter. Two shortest regions of the overlap of the deletions (SROs) were(More)
Numerous studies have identified the roof plate as an important signaling center controlling dorsal interneuron specification and differentiation in the developing spinal cord. Currently, the molecular pathways of roof plate formation and function are poorly understood. We determined that the LIM-homeodomain transcription factor Lmx1b is sufficient to(More)
Dandy-Walker malformation (DWM), the most common human cerebellar malformation, has only one characterized associated locus. Here we characterize a second DWM-linked locus on 6p25.3, showing that deletions or duplications encompassing FOXC1 are associated with cerebellar and posterior fossa malformations including cerebellar vermis hypoplasia (CVH),(More)
During embryogenesis, the isthmic organizer, a well-described signaling center at the junction of the mid-hindbrain, establishes the cerebellar territory along the anterior/posterior axis of the neural tube. Mechanisms specifying distinct populations within the early cerebellar anlage are less defined. Using a newly developed gene expression map of the(More)
Numerous studies have identified the roof plate as an embryonic signaling center critical for dorsal central nervous system patterning, but little is known about mechanisms that control its formation and its separation from clonally related neural crest cells and dI1 sensory interneurons. We demonstrate that the LIM homeodomain transcription factor, Lmx1a,(More)
Heterozygous deletions encompassing the ZIC1;ZIC4 locus have been identified in a subset of individuals with the common cerebellar birth defect Dandy-Walker malformation (DWM). Deletion of Zic1 and Zic4 in mice produces both cerebellar size and foliation defects similar to human DWM, confirming a requirement for these genes in cerebellar development and(More)