Xenopus Kielin: A dorsalizing factor containing multiple chordin-type repeats secreted from the embryonic midline

Xenopus Kielin: A dorsalizing factor containing multiple chordin-type repeats secreted from the embryonic midline

Departments of ^*Biological Sciences and ^†Neurology, Kyoto University Faculty of Medicine, Sakyo, Kyoto 606-8501 Japan; ^§Department of Medical Embryology and Neurobiology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo, Kyoto 606-8507 Japan; and ^¶Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Corporation (JST), Seikacho 619-0237 Japan

Edited by John B. Gurdon, University of Cambridge, Cambridge, United Kingdom, and approved March 9, 2000 (received for review January 18, 2000)

Abstract

The midline tissues are important inductive centers of early vertebrate embryos. By signal peptide selection screening, we isolated a secreted factor, Kielin, which contains multiple cys-rich repeats similar to those in chordin (Chd). Expression of Kielin starts at midgastrula stages in the notochord and is detected in the floor plate of neurula embryos. Kielin is induced in mesoderm and in ectoderm by nodal-related genes. Chd is sufficient to activate Kielin expression in mesoderm whereas Shh or HNF-3β in addition to Chd is required for induction in ectoderm. Kielin has a distinct biological activity from that of Chd. Injection of Kielin mRNA causes dorsalization of ventral marginal zone explants and expansion of MyoD expression in neurula embryos. Unlike Chd, Kielin does not efficiently induce neural differentiation of animal cap ectoderm, suggesting that the activity of Kielin is not simply caused by BMP4 blockade. Kielin is a signaling molecule that mediates inductive activities of the embryonic midline.

Footnotes

↵ ‡ M.M. and K.M. contributed equally to this work.
↵ ‖ To whom reprint requests should be addressed at: Department of Medical Embryology and Neurobiology, Institute for Frontier Medical Sciences, Kyoto University, Shogo-in, Sakyo, Kyoto 606-8507, Japan. E-mail: sasai{at}frontier.kyoto-u.ac.jp.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AB026192).
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.090020497.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.090020497
Abbreviations:

Chd,

chordin;

BMP,

bone morphogenetic protein;

CNS,

central nervous system;

VMZ,

ventral marginal zone;

vWM,

von Willebrand factor;

NCAM,

neural cell adhesion molecule