Maternal xNorrin Controls Early Neuroectoderm Specification in Xenopus

Initiation of central nervous system in early animal embryos is one of the most important development processes. The first step of the process is to generate neural precursors from early ectoderm. The neural precursors originate from dorsal ectoderm cells, which acquire a neural fate during dorsal-ventral axis formation. Previous studies indicate that β-catenin is a key molecule for dorsal-ventral specification, whose activation in all dorsal cells relies on maternal Wnt11. However, it remains unknown whether other maternally secreted factors specifically contribute to β-catenin activation in the dorsal ectoderm.

Using Xenopus laevis as a model system, scientists in Dr. Jian Zhang’s laboratory from Institute of Genetics and Developmental Biology, the Chinese Academy of Sciences discovered that maternal Xenopus Norrin (xNorrin) is required for β-catenin activation in the dorsal ectoderm. More importantly xNorrin functions upstream of all known zygotic neural inducers, and is essential for neural precursor formation in the head. Without xNorrin activity, anterior structures, including brain structures are severely diminished suggesting that xNorrin is an essential maternal factor for central nervous system development.

Previous molecular and biochemical analyses revealed that xNorrin encodes a ligand for the receptors in canonical Wnt signaling pathway. Now, Dr. Zhang’s group revealed that xNorrin also has inhibitory activities towards BMP/Nodal-related signaling. More importantly, a subset of Norrin derivatives of human Norrie disease patients retain Wnt activation but show defective inhibition of BMP/Nodal-related signaling, suggesting loss of BMP/Nodal inhibition may be the cause of the disease.

This work with Dr.Su-hong Xu as the first author has been published online in PLoS BIOLOGY (doi:10.1371/journal.pbio.1001286). This research was supported by grants from Chinese Academy of Sciences, Ministry of Science and Technology, and National Natural Science Foundation of China.

AUTHOR CONTACT:

Jian Zhang, Ph.D.

Institute of Genetics and Developmetnal Biology, Chinese Academy of Sciences, Beijing, China.

E-mail: jiangzhang84@genetics.ac.cn