Midline Structures (midline + structure)

Distribution by Scientific Domains

Selected Abstracts

Xenopus aristaless-related homeobox (xARX) gene product functions as both a transcriptional activator and repressor in forebrain development

Daniel W. Seufert
Abstract Mutations in the aristaless-related homeobox (ARX) gene have been found in patients with a variety of X-linked mental retardation syndromes with forebrain abnormalities, including lissencephaly. Arx is expressed in the developing mouse, Xenopus, and zebrafish forebrain. We have used whole-mount in situ hybridization, overexpression, and loss-of-function studies to investigate the involvement of xArx in Xenopus brain development. We verified that xArx is expressed in the prospective diencephalon, as the forebrain is patterned and specified during neural plate stages. Expression spreads into the ventral and medial telencephalon as development proceeds through neural tube and tadpole stages. Overexpression of xArx resulted in morphological abnormalities in forebrain development, including loss of rostral midline structures, syn- or anophthalmia, dorsal displacement of the nasal organ, and ventral neural tube hyperplasia. Additionally, there is a delay in expression of many molecular markers of brain and retinal development. However, expression of some markers, dlx5 and wnt8b, was enhanced in xArx -injected embryos. Loss-of-function experiments indicated that xArx was necessary for normal forebrain development. Expansion of wnt8b expression depended on xArx function as a transcriptional repressor, whereas ectopic expression of dlx5, accompanied by development of ectopic otic structures, depended on function of Arx as a transcriptional activator. These results suggest that Arx acts as a bifunctional transcriptional regulator in brain development. Developmental Dynamics 232:313,324, 2005. 2004 Wiley-Liss, Inc. [source]

Developmental analysis of activin-like kinase receptor-4 (ALK4) expression in Xenopus laevis

Yumei Chen
Abstract The type I transforming growth factor-beta (TGF,) receptor, activin-like kinase-4 (ALK4), is an important regulator of vertebrate development, with roles in mesoderm induction, primitive streak formation, gastrulation, dorsoanterior patterning, and left,right axis determination. To complement previous ALK4 functional studies, we have analyzed ALK4 expression in embryos of the frog, Xenopus laevis. Results obtained with reverse transcriptase-polymerase chain reaction indicate that ALK4 is present in both the animal and vegetal poles of blastula stage embryos and that expression levels are relatively constant amongst embryos examined at blastula, gastrula, neurula, and early tail bud stages. However, the tissue distribution of ALK4 mRNA, as assessed by whole-mount in situ hybridization, was found to change over this range of developmental stages. In the blastula stage embryo, ALK4 is detected in cells of the animal pole and the marginal zone. During gastrulation, ALK4 is detected in the outer ectoderm, involuting mesoderm, blastocoele roof, dorsal lip, and to a lesser extent, in the endoderm. At the onset of neurulation, ALK4 expression is prominent in the dorsoanterior region of the developing head, the paraxial mesoderm, and midline structures, including the prechordal plate and neural folds. Expression in older neurula stage embryos resolves to the developing brain, somites, notochord, and neural crest; thereafter, additional sites of ALK4 expression in tail bud stage embryos include the spinal cord, otic placode, developing eye, lateral plate mesoderm, branchial arches, and the bilateral heart fields. Together, these results not only reflect the multiple developmental roles that have been proposed for this TGF, receptor but also define spatiotemporal windows in which ALK4 may function to modulate fundamental embryological events. Developmental Dynamics 232:393,398, 2005. 2004 Wiley-Liss, Inc. [source]

Mediolateral intercalation in planarians revealed by grafting experiments

Yumi Saito
Abstract We investigated how planarians organize their left,right axis by using ectopic grafting. Planarians have three body axes: anteroposterior (A-P), dorsoventral (D-V), and left,right (L-R). When a small piece is implanted into an ectopic region along the A-P and D-V axes, intercalary structures are always formed to compensate for positional gaps. There are two hypotheses regarding L-R axis formation in this organism: first, that the left and right sides of the animal may be recognized as different parts, and L-R intercalation can induce midline structures (asymmetry hypothesis); second, that both sides may have symmetrical positional values, and mediolateral (M-L) intercalation creates positional values along the L-R axis (symmetry hypothesis). We performed ectopic grafting experiments in the head region of the planarian, Dugesia japonica, to examine these hypotheses. A left lateral fragment containing a left auricle was implanted into the medial region of the host. Ectopic structures were always formed only on the left side of the graft, where lateral tissues abutted onto the medial tissues. However, no morphologic change was induced on the right side of the graft, where left-sided tissues faced onto right-sided tissues. Molecular marker analyses indicated that ectopic structures formed on the left side of the graft were induced by M-L intercalation, supporting the "symmetry hypothesis." When the midline tissues were implanted into a lateral region, they induced a complete ectopic head, demonstrating that M-L intercalation may be sufficient to establish the L-R axis in planarians. Developmental Dynamics 226:334,340, 2003. 2003 Wiley-Liss, Inc. [source]

Increased self-focus in major depressive disorder is related to neural abnormalities in subcortical-cortical midline structures

Simone Grimm
Abstract Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and reflect upon their self, which has been described as increased self-focus. Although subcortical-cortical midline structures have been associated with reflection and introspection of oneself in healthy subjects, the neural correlates of the abnormally increased attribution of negative emotions to oneself, i.e. negative self-attribution, as hallmark of the increased self-focus in MDD remain unclear. The aim of the study was, therefore, to investigate the neural correlates during judgment of self-relatedness of positive and negative emotional stimuli thereby testing for emotional self-attribution. Using fMRI, we investigated 27 acute MDD patients and compared them with 25 healthy subjects employing a paradigm that focused on judgment of self-relatedness when compared with mere perception of the very same emotional stimuli. Behaviourally, patients with MDD showed significantly higher degrees of self-relatedness of specifically negative emotional stimuli when compared with healthy subjects. Neurally, patients with MDD showed significantly lower signal intensities in various subcortical and cortical midline regions like the dorsomedial prefrontal cortex (DMPFC), supragenual anterior cingulate cortex, precuneus, ventral striatum (VS), and the dorsomedial thalamus (DMT). Signal changes in the DMPFC correlated with depression severity and hopelessness whereas those in the VS and the DMT were related to judgment of self-relatedness of negative emotional stimuli. In conclusion, we present first evidence that the abnormally increased negative self-attribution as hallmark of the increased self-focus in MDD might be mediated by altered neural activity in subcortical-cortical midline structures. Hum Brain Mapp, 2009. 2008 Wiley-Liss, Inc. [source]

Neuroimaging advances in holoprosencephaly: Refining the spectrum of the midline malformation,

Jin S. Hahn
Abstract Holoprosencephaly (HPE) is a complex congenital brain malformation characterized by failure of the forebrain to bifurcate into two hemispheres, a process normally completed by the fifth week of gestation. Modern high-resolution brain magnetic resonance imaging (MRI) has allowed detailed analysis of the cortical, white matter, and deep gray structural anomalies in HPE in living humans. This has led to better classification of types of HPE, identification of newer subtypes, and understanding of the pathogenesis. Currently, there are four generally accepted subtypes of HPE: alobar, semilobar, lobar, and middle interhemispheric variant. These subtypes are defined primarily by the degree and region of neocortical nonseparation. Rather than there being four discrete subtypes of HPE, we believe that there is a continuum of midline neocortical nonseparation resulting in a spectrum disorder. Many patients with HPE fall within the border zone between the neighboring subtypes. In addition, there are patients with very mild HPE, where the nonseparation is restricted to the preoptic (suprachiasmic) area. In addition to the neocortex, other midline structures such as the thalami, hypothalamic nuclei, and basal ganglia are often nonseparated in HPE. The cortical and subcortical involvements in HPE are thought to occur due to a disruption in the ventral patterning process during development. The severity of the abnormalities in these structures determines the severity of the neurodevelopmental outcome and associated sequelae. 2010 Wiley-Liss, Inc. [source]

Sequential developmental changes in holoprosencephalic mouse embryos exposed to ethanol during the gastrulation period,

Daisuke Higashiyama
Abstract BACKGROUND: Prenatal exposure to ethanol induces holoprosencephalic malformations in both humans and laboratory animals. However, its teratogenic window for inducing holoprosencephaly is narrow, and the teratogenic mechanism is not well understood. In the present study, we examined the morphological changes in the craniofacial structures of mouse embryos/fetuses at intervals following ethanol treatment and evaluated gene expression patterns in the embryos. METHODS: Pregnant C57BL/6J mice were given two doses of ethanol (30 mg/kg in total) on the morning (7:00 and 11:00 AM) of day 7. The fetuses were observed at E10.5 and E15.5 grossly and/or histologically. The expression of Shh and Nkx2.1 gene transcripts was examined at E8.5 by in situ hybridization. RESULTS: Gross and histological abnormalities of the brain and face were found in ethanol-exposed fetuses, and their midline structures were most frequently affected. The midline commissural fibers were often lacking in ethanol-exposed fetuses, even in those cases without external gross malformations. In situ hybridization revealed down-regulation of Shh and Nkx2.1 genes in ethanol-exposed embryos. CONCLUSIONS: The results indicate that ethanol may perturb the expression of some developmental genes at a critical stage of embryonic development and induce holoprosencephaly and other midline craniofacial malformations, including histological brain abnormalities. Birth Defects Research (Part A), 2007. 2007 Wiley-Liss, Inc. [source]