Expression of neural crest markers by human embryonic stem cells: an introductory project

Introduction: Neural crest cells make up a transient migratory population of cells found in all vertebrate embryos. Great advances have been made over the past 20 years in clarifying the molecular basis of neural crest induction and, although much still remains unclear, it appears that it is a process involving several factors acting at different stages of embryogenesis. In the future, an understanding of the precise mechanisms involved in orofacial development, even at the earliest stages, may well be of use to all clinicians interested in the management of these tissues. Aim: The present study was designed to determine if the early addition of noggin (a bone morphogenetic protein (BMP) antagonist) and/or the late addition of BMP4 would increase the expression of the transcription factors: Msx-1, Snail, Slug and Pax-7. Method: This involved an assessment of the effects of early addition (Days 0 to 3) of noggin and/or the late addition (Days 4 to 7) of BMP4 on the expression of the neural crest markers by human embryonic stem cells, co-cultured for eight days on a feeder layer of mouse PA6 cells. Results and conclusions: The expression of the neural crest markers Pax-7, Msx-1, Slug, and Snail by human embryonic stem cells is likely to be affected by the addition of noggin and BMP4. Not all of these effects will necessarily be significant. The late addition of BMP4 is likely to significantly increase the expression of Pax-7 by human embryonic stem cells (hESCs), when compared with the effects of co-culturing with stromal cell-derived inducing activity, alone. The early addition of noggin and the late addition of BMP4 are likely to significantly increase the expression of Msx-1 by hESCs, when compared with the late addition of BMP4, alone. The hESC results support those from animal ESC studies that the late addition of BMP4, especially, may result in the differentiation of neural crest precursors.