Developmental Biology Select

In this issue, we present Developmental Biology Select in which we discuss recent papers that unravel the parts played by morphogens in diverse processes including stem cell maintenance and cellular differentiation. The new studies suggest that in stem cells, global regulators of transcription and RNA stability could work in parallel with morphogens to control self renewal and differentiation. In addition, two recent screens, one examining miRNA expression and the other using RNAi, identify factors that impact morphogen expression and downstream signaling events. Morphogens, such as hedgehog and bone morphogenetic proteins (BMPs), promote the self renewal of germline stem cells in the Drosophila ovary. Recent work by Xi and Xie (2005) shows that a chromatin remodeling factor, imitation SWI (ISWI), is required for germline stem cells to respond appropriately to BMPs. ISWI promotes nucleosomal sliding (the repositioning of nucleosomes without dissociation from the DNA) and is involved in transcriptional regulation. Germline stem cells of the fly ovary that lack ISWI are rapidly lost because of a failure to repress differentiation. In defining the mechanism for the loss of germline stem cells, Xi and Xie (2005) show that the transcriptional response to BMPs is altered in iswi mutant germline stem cells. For example, transcription of Daughters against dpp (Dad) was frequently misregulated in the mutant germline stem cells compared to their wild-type counterparts. Moreover , transcription of a gene that promotes differentiation, called bag of marbles (bam), is often upregulated in the mutant germline stem cells, whereas bam expression is tightly regulated in the wild-type germline. Because BMP signal transduction is apparently normal in germline stem cells that lack ISWI, it seems that ISWI may work in parallel with BMP signaling and may control the transcriptional landscape upon which BMP acts. In contrast, loss of Domino (Dom), a chromatin remodeling factor that promotes exchange of phosphorylated histone proteins with their unmodified counterparts, had no detectable effect on germline stem cells. Instead, the self renewal of somatic stem cells in the ovary, which give rise to the follicle cells that surround the oocyte, was disrupted in Dom fly mutants. This finding implies that there are different mechanisms by which global transcription is regulated in somatic versus germline stem cell populations of the fly ovary. As these chromatin remodeling factors are highly conserved evolutionarily, it will be interesting to determine whether vertebrate homologs of Dom and ISWI have similar functions in vertebrate stem cells. …