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Symposium 1: Regulation of Neural Development by BMP and Activin Family Members. BMP regulation of stem cell differentiation
Author(s) -
Kessler J. A.,
Gomes W.,
Guha U.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.47_1.x
Subject(s) - stem cell , neurogenesis , biology , microbiology and biotechnology , neural stem cell , cellular differentiation , subventricular zone , transcription factor , bone morphogenetic protein , bone morphogenetic protein 4 , genetics , gene
The effects of BMP family members on stem cell lineage commitment depend upon the developmental age of the stem cell. BMP4 promotes apoptosis of early ventricular zone (VZ) stem cells, neuronal differentiation of later stage VZ cells, and astroglial differentiation of subventricular zone (SVZ) cells. BMP4 inhibits oligodendroglial lineage commitment at all stages of development. The effects of BMP4 in promoting commitment to a specific lineage reflect active suppression of alternate lineages by transcriptional inhibitors including ID and HEY family members and others. For example, BMP mediated increases in ID expression in SVZ stem cells suppress both oligodendroglial and neuronal differentiation. Similarly HEY 1 expression in SVZ cells suppresses neuronal differentiation, whereas HEYL expression by VZ cells inhibits glial differentiation and promotes neurogenesis. The differing effects of the BMPs on VZ and SVZ stem cells reflect also differences in the complement of transcription factors that are expressed. For example, VZ stem cells express high levels of neurogenin and HEY L whereas SVZ stem cells express lower levels of these factors but higher levels of HEY1. Thus lineage commitment by stem cells reflects interplay among stimulatory and inhibitory transcription factors, and responses to the BMPs depend upon the repertoire of transcription factors already expressed by the cell.