This laboratory is concerned with analyzing the cellular and molecular events underlying the formation, cell lineage decisions and migration of neural crest cells. The neural crest is a population of migratory cells, arising from the ectoderm of vertebrate embryos, which gives rise to a diverse range of cell types. Following neurulation, neural crest cells emerge from the neural tube and undergo extensive movements along pathways that often are characteristic of their axial level of origin. After migration, these assume one of a number of possible fates, ranging from neurons and glia of the peripheral nervous system to pigment cells and cells of the facial skeleton. What dictates the cell lineage decisions of these cells into one of numerous possible derivatives and what controls the precise and stereotypic pattern of neural crest migration? These areas represent the focus of my research.
It has been classically assumed that the neural crest is a segregated population in the early ectoderm, lying between the neural plate and presumptive epidermis. However, our recent studies on avian embryos show that individual precursor cells within the "neural folds" can form neural tube (central nervous system), neural crest (peripheral nervous system) and epidermal derivatives. This led us to explore the interactions that impart the potential to form the neural crest. Interestingly, we found that neural crest cells are generated when epidermis and neural plate are juxtaposed--a classical type of embryonic induction. Our current goal is to characterize the inductive interactions that lead to formation of the neural crest and to examine how regional differences arise in the neural crest populations along the rostrocaudal axis.
With respect to neural crest migrations, we are examining the mechanisms controlling cell movement by manipulating the environment using reagents that block specific cell-cell and cell-matrix interactions as well as ectopic expression of molecules of interest by retrovirally-mediated gene transfer. We can directly observe the effects of disrupting cell interactions on neural crest cell guidance by preparing trunk explants of living embryos in which neural crest cells are labeled with a membrane intercalating dye. Importantly, we have found that inhibitory cues inherent to the somites and notochord prevent neural crest cells from entering these domains. In addition, cell-matrix interactions mediated by integrins and extracellular matrix molecules are required for normal neural crest cell migration. Our goal is to identify interactions that are important for cell migration that subsequently leads to segmentation of the peripheral nervous system.
These studies shed important light on the mechanisms of neural crest formation and migration. Because neural crest cells are involved in a variety of birth defects and cancers such as neurofibromatosis, melanoma, neuroblastoma, our results on the normal mechanisms of neural crest development provide important clues regarding the mistakes that may lead to abnormal development or loss of the differentiated state.
2012 Women in Cell Biology Senior Award
2009 Fellow, American Academy of Arts &Science
International Society for Differentiation (President, 2013-14)
International Society for Developmental Biology (Secretary, 2010-13)
American Society for Cell Biology (Member of Council (1994-1997)
Gordon Research Conferences (Board of Directors, 2006-2013-Chair, 2012)
Sontag Foundation (Scientific Advisory Board, 2006 to present)
Simoes-Costa, M., Tan-Cabugao, J, Antoshechkin I, Sauka-Spengler, T., Bronner, M.E. (2013) Transcriptome analysis reveals novel players in the cranial neural crest gene regulatory network. Genome Res. (in press).
Barembaum, M. and Bronner, M. E. (2013) Identification and dissection of a key enhancer mediating cranial neural crest specific expression of transcription factor, Ets-1. Dev. Biol. (in press).
Hochgreb-Hagele, T. and Bronner, M.E. (2013) Zebrafish stem/progenitor factor msi2b exhibits two phases of activity mediated by different splice variants. Stem Cells (in press).
Simões-Costa M, Bronner ME. (2013) Insights into neural crest development and evolution from genommic analysis. Genome Res. 23, 1069-80
Saxena, A., Peng, B. and Bronner, M.E. (2013) Sox10-dependent neural crest origin for olfactory microvillous neurons. eLife e00336.
Smith, J., et al., (2013) Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. Nat Genet. 45, 415-21.
Hochgreb-Hägele, T., and Bronner, M.E. (2013) A novel FoxD3 gene trap line reveals neural crest precursor movement and a role for FoxD3 in their specification. Dev. Biol. 375, 1-11.
Simoes-Costa, M., McKeown, S., Tan-Cabugoa, J., Sauka-Spengler, T. and Bronner, M.E. (2012) Dynamic and differential regulation of stem cell factor FoxD3 in the neural crest is encrypted in the genome PLoS Genetics e1003142.
Green SA, Bronner ME. (2012) Gene duplication and the early evolution of neural crest development. Semin Cell Dev Biol. S1084-9521(12)00230-3
Hu, N., Strobl-Mazzulla, P., Sauka-Spengler,T., Bronner,M.E. (2012) DNA methyltransferase3A as a molecular switch mediating the neural tube to neural crest fate transition. Genes and Development 26, 2380-5.
Jayasena C.S., and Bronner, M.E. (2012) Rbms3 functions in craniofacial development by post-transcriptionally modulating TGFß signaling. J. Cell Biol. 199, 453-66.
Strobl-Mazzulla, P. and Bronner, M.E. (2012) A PHD12-Snail2 repressive complex epigenetically mediates neural crest epithelial to mesenchymal transition. J. Cell Biol. 198, 999-1010.
Kerosuo L, Bronner-Fraser M. (2012) What is bad in cancer is good in the embryo importance of EMT in neural crest development. Semin Cell Dev Biol. 23, 320-32