Endogenous bone morphogenetic protein antagonists regulate mammalian neural crest generation and survival

Abstract

We demonstrate here that Chordin and Noggin function as bone morphogenetic protein (BMP) antagonists in vivo to promote mammalian neural crest development. Using Chrd and Nog single and compound mutants, we find that Noggin has a major role in promoting neural crest formation, in which Chordin is partially redundant. BMP signaling is increased in dorsal tissues lacking Noggin and is further increased when Chordin is also absent. The early neural crest domain is expanded with decreased BMP antagonism in vivo. Noggin and Chordin also regulate subsequent neural crest cell emigration from the neural tube. However, reduced levels of these BMP antagonists ultimately result in perturbation of neural crest cell derived peripheral nervous system and craniofacial skeletal elements. Such defects reflect, at least in part, a function to limit apoptosis in neural crest cells. Noggin and Chordin, therefore, function together to regulate both the generation and survival of neural crest cells in mammalian development. Developmental Dynamics 235:2507-2520, 2006.

Geminin Is Required for Epithelial to Mesenchymal Transition at Gastrulation

“…The striking lack of Geminin in the epidermal ectoderm suggests that Geminin may function in the ectoderm like other preneural genes, such as Sox3 and Zic2 that are required for the induction of neural tissue by BMP inhibition, thereby positioning the neural-epidermal ectodermal border [54,73], consistent with observations that overexpression increases and reductions in Geminin reduce the size of the neural plate in Xenopus [7], Zebrafish [49], and Drosophila [10] embryos. Geminin may then maintain proliferation in the neural ectoderm and prevent premature expression of genes involved in faterestriction [34,35,74].…”

“…Neural crest emigration has been considered a second gastrulation event [53], and neural crest versus epidermal identity is determined by BMP and Wnt signaling; intermediate levels of BMP signaling position the border [54][55][56]. A second mesodermal Wnt signal [57] with BMP then activates Msx1,2 gene expression [58], which induce expression of Twist1, Snail1, and Slug [59] that then induce p21, and downregulate E-Cadherin expression to promote EMT.…”

The Bone Morphogenetic Protein Antagonist Noggin Regulates Mammalian Cardiac Morphogenesis

“…9 Because the absence of Noggin increases neural crest production, 29 we tested whether incorporation of migrating NCCs might be partially responsible for the larger OFT cushion phenotype. To visualize the neural crest-derived cell population in the cushion, we bred the neural crest-specific Wnt1-Cre driver into the Cre-dependent Rosa26R-GFP reporter line, as described.…”

Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest

“…139,209 Consistent with these observations, NC cells delaminate precociously and in greater amounts in mouse embryo lacking Noggin. 210 Additional studies in the chick embryo suggest that Noggin expression is under the control of the paraxial mesoderm. Specifically, the dorsomedial region of the dissociating somite was proposed to be the source of an inhibitory factor of unknown nature that downregulates Noggin expression in the dorsal neural tube.…”