BMP signaling in mammalian neural tube development

Duke University, Durham NC

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Abstract

DESCRIPTION (provided by applicant): Congenital malformations involving the neural tube are among the most common birth defects worldwide. The mouse has become an excellent system to study these malformations due to the similarities to human development and the genetics available to study developmental processes in the mouse. Several lines of evidence implicate Bone Morphogenetic Proteins (BMPs) in neurulation. BMP activity (particularly that of the BMP 2/4 signaling pathway) is implicated in forming the neural plate and neural crest as well as patterning the neural tube (formed from the neural plate) along the dorsal-ventral axis, particularly with respect to neuronal progenitors. BMP signaling has been difficult study in the mouse, however, as many null mutations are lethal before the process of neurulation. We aim to address the role of BMPs in dorsal neural tube development using two different approaches. The BMP antagonism gene, Noggin, is expressed in the neural tube and loss of function in the mouse results in severe neural tube defects resembling human malformations. We will further study the role of noggin in development and patterning of the neural tube to understand the basis of these defects. To address BMP signaling, we will use the Cre-Lox tissue specific recombination system to inhibit BMP signal transduction in the dorsal neural tube. We hypothesize this will result in severe defects in neurulation, patterning and/or neural crest induction, uncovering the specific contributions of BMP2/4 signaling to neural tube elaboration.