Decision letter: Dynamic BMP signaling polarized by Toll patterns the dorsoventral axis in a hemimetabolous insect

Toll-dependent patterning of the dorsoventral axis in Drosophila represents one of the best understood gene regulatory networks. However, its evolutionary origin has remained elusive. Outside the insects Toll is not known for a patterning function, but rather for a role in pathogen defense. Here, we show that in the milkweed bug Oncopeltus fasciatus, whose lineage split from Drosophila's more than 350 million years ago, Toll is only required to polarize a dynamic BMP signaling network. A theoretical model reveals that this network has self-regulatory properties and that shallow Toll signaling gradients are sufficient to initiate axis formation. Such gradients can account for the experimentally observed twinning of insect embryos upon egg fragmentation and might have evolved from a state of uniform Toll activity associated with protecting insect eggs against pathogens.

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BMP signaling patterns the dorsal and intermediate neural tube via regulation of homeobox and helix-loop-helix transcription factors

Development ◽

10.1242/dev.129.10.2459 ◽

2002 ◽

Vol 129 (10) ◽

pp. 2459-2472 ◽

Cited By ~ 15

Author(s):

John R. Timmer ◽

Charlotte Wang ◽

Lee Niswander

Keyword(s):

Transcription Factors ◽

Neural Tube ◽

Transforming Growth Factor ◽

Cell Types ◽

Neural Cell ◽

Bmp Signaling ◽

Expression Domain ◽

Cell Identity ◽

Dorsoventral Axis ◽

Helix Loop Helix

In the spinal neural tube, populations of neuronal precursors that express a unique combination of transcription factors give rise to specific classes of neurons at precise locations along the dorsoventral axis. Understanding the patterning mechanisms that generate restricted gene expression along the dorsoventral axis is therefore crucial to understanding the creation of diverse neural cell types. Bone morphogenetic proteins (BMPs) and other transforming growth factor β (TGFβ) proteins are expressed by the dorsal-most cells of the neural tube (the roofplate) and surrounding tissues, and evidence indicates that they play a role in assigning cell identity. We have manipulated the level of BMP signaling in the chicken neural tube to show that BMPs provide patterning information to both dorsal and intermediate cells. BMP regulation of the expression boundaries of the homeobox proteins Pax6, Dbx2 and Msx1 generates precursor populations with distinct developmental potentials. Within the resulting populations, thresholds of BMP act to set expression domain boundaries of developmental regulators of the homeobox and basic helix-loop-helix (bHLH) families, ultimately leading to the generation of a diversity of differentiated neural cell types. This evidence strongly suggests that BMPs are the key regulators of dorsal cell identity in the spinal neural tube.

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Jagged-Notch, Edn1, and Bmp signaling define discrete preskeletal domains along the dorsoventral axis of the vertebrate face

Developmental Biology ◽

10.1016/j.ydbio.2011.05.059 ◽

2011 ◽

Vol 356 (1) ◽

pp. 118

Author(s):

Gage Crump ◽

Elizabeth Zuniga ◽

Marie Rippen ◽

Courtney Alexander ◽

Tom Schilling

Keyword(s):

Bmp Signaling ◽

Dorsoventral Axis

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The role of tolloid/mini fin in dorsoventral pattern formation of the zebrafish embryo

Development ◽

10.1242/dev.126.14.3119 ◽

1999 ◽

Vol 126 (14) ◽

pp. 3119-3130 ◽

Cited By ~ 14

Author(s):

S.A. Connors ◽

J. Trout ◽

M. Ekker ◽

M.C. Mullins

Keyword(s):

Gene Expression ◽

Neural Development ◽

Zebrafish Embryo ◽

Bmp Signaling ◽

Mutant Phenotype ◽

Chromosomal Mapping ◽

Activity Levels ◽

Dorsoventral Axis ◽

Gene Characterization

A highly conserved TGF-β signaling pathway is involved in the establishment of the dorsoventral axis of the vertebrate embryo. Specifically, Bone Morphogenetic Proteins (Bmps) pattern ventral tissues of the embryo while inhibitors of Bmps, such as Chordin, Noggin and Follistatin, are implicated in dorsal mesodermal and neural development. We investigated the role of Tolloid, a metalloprotease that can cleave Chordin and increase Bmp activity, in patterning the dorsoventral axis of the zebrafish embryo. Injection of tolloid mRNA into six dorsalized mutants rescued only one of these mutants, mini fin. Through chromosomal mapping, linkage and cDNA sequence analysis of several mini fin alleles, we demonstrate that mini fin encodes the tolloid gene. Characterization of the mini fin mutant phenotype reveals that Mini fin/Tolloid activity is required for patterning ventral tissues of the tail: the ventral fin, and the ventroposterior somites and vasculature. Gene expression studies show that mfn mutants exhibit reduced expression of ventrally restricted markers at the end of gastrulation, suggesting that the loss of ventral tail tissues is caused by a dorsalization occurring at the end of gastrulation. Based on the mini fin mutant phenotype and the expression of tolloid, we propose that Mini fin/Tolloid modifes the Bmp activity gradient at the end of gastrulation, when the ventralmost marginal cells of the embryo are in close proximity to the dorsal Chordin-expressing cells. At this time, unimpeded Chordin may diffuse to the most ventral marginal regions and inhibit high Bmp activity levels. In the presence of Mini fin/Tolloid, however, Chordin activity would be negatively modulated through proteolytic cleavage, thereby increasing Bmp signaling activity. This extracellular mechanism is amplified by an autoregulatory loop for bmp gene expression.

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