Lost your password?
Are you a new user?

Molécula Faltante Tiene Papel Importante en el Desarrollo de la Anormalidad Cerebral

Missing Molecule Has Important Role in a Developmental Brain Abnormality


New Haven, Conn. — A molecule that is part of a complex signaling network in the developing brain plays a critical role in periventricular heterotopia (PVH), a congenital brain malformation, Yale School of Medicine researchers report in Neuron.

PVH often leads to a variety of neurological disorders such as epilepsy, mental retardation, and learning or memory deficits. It has many environmental and genetic causes, but is most commonly due to mutations in the gene Filamin-A.

Pasko Rakic, professor and chair of neurobiology, director of the Kavli Institute for Neuroscience, and senior author of the study, said that up until now the molecular mechanisms that regulate Filamin-A in the brain are not well understood. This study shows that the molecule MEKK4 regulates Filamin-A and its loss contributes to PVH.

“We show that MEKK4 deficiency leads to both a breakdown in the lining of the fetal ventricles and abnormally high levels of Filamin-A within the proliferative areas,” Rakic said. Using advanced molecular methods, the researchers showed that the loss of MEKK4 can result in an excess of Filamin-A, and inhibit neuronal migration.

The grey matter of human cerebral cortex contains over two billion neurons, but none of them are produced in the cortex itself. Cortical neurons are born near the lining of the fluid-filled ventricles deep within the fetal brain and after their last division migrate to their increasingly distant final destination in the outer cortex. To do this, migrating neurons must climb along transient scaffold of radial glial fibers that span the developing cortex.

“Upon reaching their final destination, neurons stop migrating and establish specific connections with other neurons,” Rakic said. “This is a dynamic and complex process that, in humans, occurs during gestation over many months and is regulated by numerous molecules, especially by those that control nuclear and cell body movement.”

The Filamin-A protein binds and organizes the intracellular contractile protein called actin, which is essential for neuronal migration. It was reported in this study that MEKK4 is important for maintaining the correct level of Filamin-A and the integrity of the ventricular surface lining, both of which contribute to the pathogenesis of PVH.

Co-authors include Matt Sarkisian, Christopher Bartley, Hongbo Chi, Fumihiko Nakamura, Kazue Hashimoto-Torii, Masaaki Toril, and Richard Flavell, chair and professor of immunobiology.

Neuron 52: 1-13 (December 7, 2006)

Jacqueline Weaver 203-432-8555

Courtesy of Yale University

The following comments are owned by whomever posted them. This site is not responsible for what they say.

Need help?

LiveZilla Live Help

 

Currently online

Error in PHP Block. Function, phpblock_anon_whosonline, does not exist.

 Visitors & Countries

Since 24-04-12 -Site Statistics

Connect & Share