The LIM adaptor protein LMO4 is an essential regulator of neural crest development

The neural crest (NC) is a population of multipotent stem cell-like progenitors that arise at the neural plate border in vertebrates and migrate extensively before giving rise to diverse derivatives. A number of components of the neural crest gene regulatory network (NC-GRN) are used reiteratively to control multiple steps in the development of these cells. It is therefore important to understand the mechanisms that control the distinct function of reiteratively used factors in different cellular contexts, and an important strategy for doing so is to identify and characterize the regulatory factors they interact with. Here we report that the LIM adaptor protein, LMO4, is a Slug/Snail interacting protein that is essential for NC development. LMO4 is expressed in NC forming regions of the embryo, as well as in the central nervous system and the cranial placodes. LMO4 is necessary for normal NC development as morpholino-mediated knockdown of this factor leads to loss of NC precursor formation at the neural plate border. Misexpression of LMO4 leads to ectopic expression of some neural crest markers, but a reduction in the expression of others. LMO4 binds directly to Slug and Snail, but not to other components of the NC-GRN and can modulate Slug-mediated neural crest induction, suggesting a mechanistic link between these factors. Together these findings implicate LMO4 as a critical component of the NC-GRN and shed new light on the control of Snail family repressors. (C) 2011 Elsevier Inc. All rights reserved.