Noelins modulate the timing of neuronal differentiation during development.
Noelins comprise a family of extracellular proteins with proposed roles in neural and neural crest development. Here, we show that a previously uncharacterized family member, Noelin-4, functions to maintain neural precursors in an undifferentiated state and biases ectoderm toward a neural fate. We show that Noelin-4 is induced by the neurogenic genes X-ngnr-1 and XNeuroD. Over-expression of Noelin-4 causes expansion of the neural plate at the expense of neural crest and epidermis. Although there is an apparent increase in the neural precursor pool, no increase was noted in differentiated neurons. Later, derivatives such as the neural tube and retina appear enlarged. We show biochemically that Noelin-4 protein is glycosylated and secreted and that it interacts with Noelin-1, an isoform previously found to promote differentiation in neuralized animal caps. Accordingly, the neural precursor expansion activity of Noelin-4 is reversed by co-expression of Noelin-1. Our finding that Noelin isoforms can bind to and antagonize one another suggests that interacting Noelin isoforms may play a role in regulating timing of differentiation.
Moreno
Tanya A
TA
Division of Biology, 139-74, California Institute of Technology, Pasadena, CA 91125, USA.
Bronner-Fraser
Marianne
M
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D006031:Glycosylation; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D011485:Protein Binding; D020033:Protein Isoforms / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction; D029867:Xenopus Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D029867:Xenopus Proteins; C101907:neurogenin, Xenopus; C508881:noelin-4 protein, Xenopus; C081451:olfactomedin