BMP signaling in mammalian neural tube development

描述（由申请人提供）：涉及 神经管是世界上最常见的出生缺陷之一。述小鼠具有 成为研究这些畸形的优秀系统， 对人类发展和遗传学的影响， 在老鼠的过程中。几条证据表明骨形态发生 神经形成中的蛋白质（BMP）。BMP活性（特别是BMP 2/4的活性） 信号通路）与神经板和神经嵴的形成有关 以及沿着沿着神经板图案化神经管（由神经板形成）， 背腹轴，特别是相对于神经元祖细胞。BMP 在小鼠中进行信号传导研究一直很困难，然而，由于许多无效的 在神经胚形成之前突变是致命的我们的目标是解决 BMPs在背神经管发育中的作用。 BMP拮抗基因Noggin在神经管中表达， 在小鼠中的功能导致类似于人类的严重神经管缺陷 畸形我们将进一步研究脑在发育中的作用， 神经管的图案，以了解这些缺陷的基础。到 为了解决BMP信号传导，我们将使用Cre-Lox组织特异性重组 系统抑制BMP信号转导的背神经管。我们 假设这将导致严重的神经形成缺陷， 和/或神经嵴诱导，揭示BMP 2/4的特异性作用 传递信号到神经管

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.