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Genetics of morphogen gradients

Nature Reviews Genetics volume 2, pages 620–630 (2001)Cite this article

Key Points

  • A morphogen is a type of signalling molecule that imparts pattern to a developmental field by acting directly on cells in a concentration-dependent manner.

  • The best-studied model system for understanding morphogen function is the Drosophila wing, where Decapentaplegic (Dpp), Wingless (Wg) and Hedgehog (Hh) proteins have been shown to act as morphogens.

  • Several models have been proposed for generating a morphogen gradient; diffusion through the extracellular space is important in trafficking of the Wg morphogen, and planar transcytosis (transcellular transport) has an important function in Dpp trafficking.

  • The activity gradient of Dpp can be visualized in situ by using an antibody that specifically recognizes phosphorylated Mothers against Dpp (Mad), a cytoplasmic signal transducer of Dpp signalling.

  • Receptor levels can regulate the distribution of receptor ligands and their activity gradients. This has been observed for the Dpp and Hh morphogens.

  • Negative regulators are involved in shaping the activity gradient at several levels.

  • Many of the molecules and molecular mechanisms that have been identified in Drosophila might also be involved in the development of vertebrate systems, although this can only be confirmed by using more rigorous genetic analysis.

Abstract

The organization of cells and tissues is controlled by the action of 'form-giving' signalling molecules, or morphogens, which pattern a developmental field in a concentration-dependent manner. As the fate of each cell in the field depends on the level of the morphogen signal, the concentration gradient of the morphogen prefigures the pattern of development. In recent years, molecular genetic studies in Drosophila melanogaster have allowed tremendous progress in understanding how morphogen gradients are formed and maintained, and the mechanism by which receiving cells respond to the gradient.

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Figure 1: Patterning a developmental field by long-range signalling.
Figure 2: Inductive signals organize neuronal cell identity along the dorsoventral axis of the neural tube.
Figure 3: Inductive activities during the development of the Drosophila wing.
Figure 4: Inductive activities of Hedgehog and Decapentaplegic.
Figure 5: The Decapentaplegic signalling pathway.
Figure 6: Ligand and activity gradient of the Decapentaplegic morphogen.
Figure 7: Models for movement of the morphogen molecule.
Figure 8: Evidence for planar transcytosis of Decapentaplegic in the wing imaginal disc.

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Acknowledgements

I thank A. Kuroiwa, H. Nakamura, S. Noji and K. Tamura for helpful suggestions. Research conducted in the T.T. laboratory was supported by grants from the Japan Society for the Promotion of Science (Research for the Future Program) and grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Tokyo, 113-0032, Japan

    Tetsuya Tabata

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  1. Tetsuya Tabata
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DATABASE LINKS

TGF-β

Hh

Wnt

Activin

BMP

Shh

FGF8

Dpp

Wg

en

sal

omb

fringe

Notch

apterous

Dll

vg

Tkv

Sax

Put

Nrt

dishevelled

armadillo

Cd2

Ptc

Sqt

shi

Rab5

Rab7

Smo

sgl

sfl

dally

dally-like

Disp

ttv

human multiple exostoses

Ihh

Ext1

Mad

Dad

mtv

Fz

Dfz2

Dfz3

Brk

Ubx

Sog

Med

Glossary

MESODERM

The third germ layer in the embryo, formed during the process of gastrulation.

SELECTOR GENES

A class of transcription factor, the products of which control the formation and identity of various morphogenetic fields.

CELL AUTONOMOUS

If the gene activity causes the effects only in the cells that express it, its function is cell autonomous; if it causes the effects in cells other than (or in addition to) those expressing it, its function is cell non-autonomous.

PLANAR TRANSCYTOSIS

A mechanism of transcellular transport within the plane of epithelium by which the molecule is internalized by endocytosis, transports intracellularly and is released to signal in the adjacent cells.

DYNAMIN

A GTPase required for clathrin-mediated endocytosis.

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Tabata, T. Genetics of morphogen gradients. Nat Rev Genet 2, 620–630 (2001). https://doi.org/10.1038/35084577

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