BMP Antagonists and Neural Induction

Abstract

In vertebrates, during the gastrula stage of embryonic development, the dorsal part of the ectoderm (the animal pole) is fated to form the neural plate, whereas the ectoderm located at the ventral side will primarily form epidermis. Embryonic factors known as BMP antagonists play a critical role in the processes of neural and epidermal induction.

Keywords: Spemann organizer; activin; BMPs; neural induction; epidermal induction

Figure 1.

Model for amphibian ectodermal patterning during gastrulation. (a) Dorsal view of a X. laevis gastrula embryo. During gastrulation, the organizer (red) secretes factors (including noggin, chordin, follistatin and Xnr3) that bind directly to, and inhibit epidermal inducers (including BMP2, BMP4 and BMP7). The border of the dorsal and ventral ectoderm is enlarged in (b). (b) In the dorsal ectoderm, factors secreted by the organizer inhibit epidermal differentiation by binding to epidermal inducers. In the ventral ectoderm, these BMP antagonists are absent and epidermal inducers can bind to their receptors without interference, and epidermal differentiation takes place. Signalling in ventral ectodermal cells downstream of these receptors is illustrated in (c). (c) BMP signalling in a ventral ectodermal cell. BMP signals are transduced via type I and II serine/threonine receptors. BMP‐activated type I receptors activate the pathway‐specific effector Smad1, which forms a complex with regulatory Smad4; this complex translocates to the nucleus where the expression of epidermal genes is induced and neural gene expression is inhibited, ultimately resulting in epidermal induction in the ventral ectoderm. In the Smad signal transduction cascade, several inhibitory Smads have been identified; Smad7 (and perhaps Smad8) inhibits signalling of TGFβ growth factors at the receptor level; Smad6 competes with Smad1 for Smad 4, resulting in an inactive Smad1/Smad6 heteromer.

close

References

Baker JC and Harland RM (1997) From receptor to nucleus: the Smad pathway. Current Opinion in Genetics and Development 7: 467–473.

Ferguson EL and Anderson KA (1992) Decapentaplegic acts as a morphogen to organize dorsal–ventral patterning in the Drosophila embryo. Cell 71: 451–461.

Harland RM and Gerhart J (1997) Formation and function of Spemann's organizer. Annual Review of Cell and Developmental Biology 13: 611–667.

Hemmati‐Brivanlou A and Melton DA (1997) Vertebrate embryonic cells will become nerve cells unless told otherwise. Cell 88: 13–17.

Hogan BL (1996) Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes and Development 10: 1580–1594.

Massagué J (1998) TGF‐β signal transduction. Annual Reviews of Biochemistry 67: 753–791.

Miya T, Morita K, Suzuki A, Ueno N and Satoh N (1997) Functional analysis of an ascidian homologue of vertebrate BMP2/BMP4 suggests its role in the inhibition of neural fate specification. Development 124: 5149–5159.

Sasai Y and De Robertis EM (1997) Ectodermal patterning in vertebrate embryos. Developmental Biology 182: 5–20.

Schier AF (1997) Genetics of neural development in zebrafish. Current Opinion in Neurobiology 7: 119–126.

Spemann H and Mangold H (1924) Über induktion von embryoanlagen durch implantation artfremder organisatoren. Roux' Archiv für Entwicklungsmechanik 100: 599–638.

Streit A, Lee KJ, Woo I et al. (1998) Chordin regulates primitive streak development and the stability of induced neural cells, but is not sufficient for neural induction in the chick embryo. Development 125: 507–519.

Suzuki A, Kaneko E, Ueno N and Hemmati‐Brivanlou A (1997) Regulation of epidermal induction by BMP2 and BMP7 signaling. Developmental Biology 189: 112–122.

Wilson PA and Hemmati‐Brivanlou A (1995) Induction of epidermis and inhibition of neural fate by BMP‐4. Nature 376: 331–333.

Wilson PA and Hemmati‐Brivanlou A (1997) Vertebrate neural induction: inducers, inhibitors, and a new synthesis. Neuron 18: 699–710.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Eggen, Bart JL, and Hemmati‐Brivanlou, Ali(Apr 2001) BMP Antagonists and Neural Induction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000805]