Bone Morphogenetic Proteins Promote Astroglial Lineage Commitment by Mammalian Subventricular Zone Progenitor Cells

Abstract

The epigenetic signals that regulate lineage development in the embryonic mammalian brain are poorly understood. Here we demonstrate that a specific subclass of the transforming growth factor beta superfamily, the bone morphogenetic proteins (BMPs), cause the selective, dose-dependent elaboration of the astroglial lineage from murine embryonic subventricular zone (SVZ) multipotent progenitor cells. The astroglial inductive effect is characterized by enhanced morphological complexity and expression of glial fibrillary acidic protein, with concurrent suppression of neuronal and oligodendroglial cell fates. SVZ progenitor cells express transcripts for the appropriate BMP-specific type I and II receptor subunits and selective BMP ligands, suggesting the presence of paracrine or autocrine developmental signaling pathways (or both). These observations suggest that the BMPs have a selective role in determining the cell fate of SVZ multipotent progenitor cells or their more developmentally restricted progeny.

Promoting remyelination for the treatment of multiple sclerosis: opportunities and challenges

“…It promotes astroglial lineage determination at the expense of oligodendrogliogenesis and inhibits the differentiation of oPCs [41,42] . More recent studies showed that BMP4 is increased during demyelination.…”

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

“…Previous studies have reported that neural progenitor cells of the adult SVZ can be driven to astrocytic phenotype by bone morphogenetic proteins (BMPs), in particular BMP-2 and BMP-4 [130][131][132]. High concentrations of these BMPs and their receptors have been identified in the SVZ of the adult rat brain [130,132] and may dictate the glial bias of newly generated cells in the adult subependyma.…”

BMP-4 induces a Smad-dependent apoptotic cell death of mouse embryonic stem cell-derived neural precursors

“…14 Similarly, BMP responses lead to apoptosis of committed populations of neural stem cells isolated from progressively older fetuses, and then to neuronal and finally glial differentiation. 15,16 We recently reported the ability of BMP-4 to efficiently promote murine ES cell differentiation towards epidermal fate and skin organogenesis in vitro. 17 In the present study, we show that a high proportion of ES cells, engaged in differentiation towards neural cell types, undergo a dose-and timedependent apoptotic cell death when treated early with BMP-4.…”