Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis.

Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, 1211 BRBII/III, 421 Curie Boulevard., Philadelphia, PA 19104-6058, USA.
Nature Cell Biology (Impact Factor: 20.06). 05/2009; 11(5):637-43. DOI: 10.1038/ncb1870
Source: PubMed

ABSTRACT Patterning the embryonic dorsoventral axis of both vertebrates and invertebrates requires signalling through bone morphogenetic proteins (BMPs). Although a well-studied process, the identity of the physiologically relevant BMP signalling complex in the Drosophila melanogaster embryo is controversial, is generally inferred from cell culture studies and has not been investigated in vertebrates. Here, we demonstrate that dorsoventral patterning in zebrafish, Danio rerio, requires two classes of non-redundant type I BMP receptors, Alk3/6 and Alk8 (activin-like kinases 3/6 and 8). We show, under physiological conditions in the embryo, that these two type I receptor classes form a complex in a manner that depends on Bmp2 and Bmp7. We found that both Bmp2-7 heterodimers, as well as Bmp2 and Bmp7 homodimers, form in the embryo. However, only recombinant ligand heterodimers can activate BMP signalling in the early embryo, whereas a combination of Bmp2 and Bmp7 homodimers cannot. We propose that only heterodimers, signalling through two distinct classes of type I receptor, possess sufficient receptor affinity in an environment of extracellular antagonists to elicit the signalling response required for dorsoventral patterning.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: L-fucose, a monosaccharide widely distributed in eukaryotes and certain bacteria, is a determinant of many functional glycans that play central roles in numerous biological processes. The molecular mechanism, however, by which fucosylation mediates these processes remains largely elusive. To study how changes in fucosylation impact embryonic development, we up-regulated N-linked fucosylation via over-expression of a key GDP-Fucose transporter, Slc35c1, in zebrafish. We show that Slc35c1 overexpression causes elevated N-linked fucosylation and disrupts embryonic patterning in a transporter activity dependent manner. We demonstrate that patterning defects associated with enhanced N-linked fucosylation are due to diminished canonical Wnt signaling. Chimeric analyses demonstrate that elevated Slc35c1 expression in receiving cells decreases the signaling range of Wnt8a during zebrafish embryogenesis. Moreover, we provide biochemical evidence that this decrease is associated with degradation of Wnt8 ligand and elevated Lrp6 coreceptor, which we show are both substrates for N-linked fucosylation in zebrafish embryos. Strikingly, slc35c1 expression is regulated by canonical Wnt signaling. These results suggest that Wnt limits its own signaling activity in part via up-regulation of a transporter, slc35c1 that promotes terminal fucosylation and thereby limits Wnt activity.
    Developmental Biology 09/2014; 395(2). DOI:10.1016/j.ydbio.2014.09.010 · 3.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the influence of bone morphogenetic protein type IA receptor [BMPR-IA (ALK3)] conditional knockout in lens on expression of bone morphogenetic protein 4 (BMP4) in lens during the development of the vertebrate eye. Cre-positive mice were mated with Cre-negative mice to generate 50% Cre-positive (conditional knockout, CKO) 4 embryos, 8 eyes and 50% Cre-negative offspring (wild type, WT) 4 embryos, 8 eyes. The embryos were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned to a thickness of 4 µm. Removal of paraffin wax and dehydrating for sections, and then the procedure of in situ hybridization was processed, BMP4 MK1784-m (BOSTER) was used, and observed the expression of BMP4 in the lens in experimental group and control group. We selected SPSS11.0 software for statistical analysis, P<0.05 showed that the difference was statistically significant. Four embryos of each genotype were examined, totally we had 8 embryos, 16 eyes. We got the uniform outcomes in all the embryos. We found ALK3 was required during lens growing, but was not essential for the formation of lens. We observed that the expression of Bmp4 in the lens was significantly reduced in all 8 ALK3 CKO lens, BMP4 expression was normal in all the 8 WT lens, P<0.01. This phenomenon became increasingly visible in accordance with embryo development. The most apparent alteration was present at stage E15.5. ALK3 is essential for lens growth. The influence of ALK3 on the expression of BMP4 is present during the development of mice lens.
    International Journal of Ophthalmology 01/2015; 8(1):57-60. DOI:10.3980/j.issn.2222-3959.2015.01.10 · 0.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The neural crest and neurogenic placodes are thought to be a vertebrate innovation that gives rise to much of the peripheral nervous system (PNS). Despite their importance for understanding chordate evolution and vertebrate origins, little is known about the evolutionary origin of these structures. Here, we investigated the mechanisms underlying the development of ascidian trunk epidermal sensory neurons (ESNs), which are thought to function as mechanosensory neurons in the rostral-dorsal trunk epidermis. We found that trunk ESNs are derived from the anterior and lateral neural plate border, as is the case in the vertebrate PNS. Pharmacological experiments indicated that intermediate levels of bone morphogenetic protein (BMP) signal induce formation of ESNs from anterior ectodermal cells. Gene knockdown experiments demonstrated that HrBMPa (60A-subclass BMP) and HrBMPb (dpp-subclass BMP) act to induce trunk ESNs at the tailbud stage and that anterior trunk ESN specification requires Chordin-mediated antagonism of the BMP signal, but posterior trunk ESN specification does not. We also found that Nodal functions as a neural plate border inducer in ascidians. Nodal signaling regulates expression of HrBMPs and HrChordin in the lateral neural plate, and consequently specifies trunk ESNs. Collectively, these findings show that BMP signaling that is regulated spatiotemporally by Nodal signaling is required for trunk ESN specification, which clearly differs from the BMP gradient model proposed for vertebrate neural induction.
    Development 09/2014; 141(20). DOI:10.1242/dev.110213 · 6.27 Impact Factor

Full-text (2 Sources)

Available from
May 19, 2014