Tài liệu Báo cáo khoa học: Bone morphogenetic proteins in the early development of zebrafish pptx

MINIREVIEW

Bone morphogenetic proteins in the early development

of zebrafish

Mariko Kondo*

Department of Biological Sciences, The University of Tokyo, Japan

Introduction

Bone morphogenetic proteins (BMPs), now widely

known for their involvement in many biological pro￾cesses, were first described for their bone morpho￾genetic activity, and thus were given their names. Four

proteins were initially identified, and one of them,

BMP1 is a metalloproteinase. The other three (BMP2,

3 and 4) are members of the transforming growth fac￾tor b (TGF-b) superfamily of secreted signaling mole￾cules. Subsequently, molecular cloning studies have

identified more than 20 members of the BMP sub￾group in the TGF-b family, from various species.

Examples of these members are decapentaplegic (Dpp)

and 60A from Drosophila, Xenopus Vg1, and BMP5-7.

Although it is not known whether all of the members

of this subgroup are involved in bone differentiation,

they control a wide range of biological processes in

various cell types, such as differentiation, cell prolifer￾ation, migration, and apoptosis.

The signaling cascade of BMPs has been inten￾sively studied, and the players have been identified

to a great extent (Fig. 1). Signals from BMPs are

mediated by BMP receptors, which also comprise a

gene family, the TGF-b receptor family. Functionally

active BMPs form dimers, which are secreted and

bind to the type I and type II receptors on the cell

surface. These receptors are serine ⁄threonine kinase

receptors with a single transmembrane domain. Bind￾ing of the ligand to the receptor complex induces

the type II receptor to phosphorylate the type I

receptor, which then leads to activation of the type I

receptor. The signal is passed on to the substrates of

the type I receptor kinase, receptor-activated Smad

proteins (R-Smads, Smad1, -2, -3, -5 and -8), which,

upon phosphorylation, are activated and bind to a

common mediator Smad (Co-Smad, Smad4).

The complexes move into the nucleus and act as

regulators of transcription. The activity of BMP is

regulated by the binding of extracellular inhibitors.

The roles and functions of BMPs in embryogenesis,

from insects to mammals, mostly during the early sta￾ges, have attracted the interest of many scientists. In

this review, I mainly focus on the recent findings using

Keywords

bone morphogenetic protein (BMP);

dorsoventral patterning; embryogenesis;

zebrafish

Correspondence

M. Kondo, Graduate School of Frontier

Sciences, The University of Tokyo,

Chiba, Japan

E-mail: [email protected]

(Received 30 November 2006, accepted

27 February 2007)

doi:10.1111/j.1742-4658.2007.05838.x

Bone morphogenetic proteins (BMPs) are known to be widely involved in

various biological processes. Many of the members of the BMP family, as

well as related factors, receptors and molecules in the BMP signaling path￾way, have been isolated, but their precise functions are still unclear. In

addition to the ‘classical’ model organism Xenopus, zebrafish, Danio rerio,

is now considered to be a suitable model organism to study the roles of the

BMP signaling pathway during embryogenesis. Mutagenesis screens have

identified a number of mutants in the pathway. Although they do not cover

the entire members of the BMP signaling cascade that are currently known,

they serve as a powerful tool to broaden our understanding of BMP func￾tions, in combination with other experimental techniques.

Abbreviations

ADMP, anti-dorsalizing morphogenetic protein; BMP, bone morphogenetic protein; TGF-b, transforming growth factor b.

*Correction added after online publication 22 May 2007: An author name has been removed at the request of the individual.

2960 FEBS Journal 274 (2007) 2960–2967 ª 2007 The Author Journal compilation ª 2007 FEBS