In Development this week (Vol. 143, Issue 19)

Here are the highlights from the current issue of Development:

Defining digit number in the limb

During vertebrate limb development, multiple mechanisms act to ensure the appropriate number, identity and positioning of digits. In both the chick and the mouse, Sonic hedgehog (Shh) signalling emanating from the posterior polarising region provides positional information and regulates tissue expansion, while a self-organising Turing-type mechanism has been proposed to account for digit number determination. However, we still have an incomplete understanding of how these mechanisms interact, and how they have been manipulated during evolution to generate different species with different numbers and types of digit. On p. 3514, Joseph Pickering and Matthew Towers use temporally defined application of the Shh inhibitor cyclopamine to the chick wing to explore these questions. They find that, surprisingly, Shh inhibition at a specific time point can lead to an increased digit number, as well as increased proliferation of the polarising region. Moreover, they observe posterior expansion of the overlying apical ectodermal ridge (AER) – the source of Fgf signalling that is also key for digit formation. The data suggest that, if Shh signalling is inhibited during this critical period, there is a switch from Shh-dependent anterior-posterior expansion to AER-dependent expansion, with consequent effects on digit number and patterning. Together, these data help to shed light on the evolutionary mechanisms resulting in the divergence in digit patterning across vertebrates.

LEUTX: promoting genome activation in the human embryo

Embryonic genome activation (EGA) is a key event in the development of all organisms – when zygotic transcription takes over from maternally provided mRNAs. Relatively little is known about the control of EGA in human embryos, which occurs at the 4- to 8-cell stage. Juha Kere and colleagues have previously found that many paired-like homeobox transcription factors are expressed in the early human embryo, and identified a 36 bp motif associated with genes upregulated at the EGA. In a follow-up study (p. 3459), the authors now characterise one of these factors, LEUTX, in more detail. LEUTX is specifically expressed in early human embryos and cell lines derived from early blastomeres, with barely detectable or absent expression in later embryos, other tissues or cell lines. The authors then use expression profiling to analyse the consequences of overexpressing LEUTX in human embryonic stem cells. LEUTX induces expression of a large number of targets, including several pluripotency-associated genes. Intriguingly, the previously identified EGA-associated 36 bp motif is significantly enriched in theLEUTX-regulated gene set; in reporter assays, LEUTX can bind this motif and promote expression. A second paired-like homeobox factor, DPRX, is a putative target of LEUTX, and in turn, appears to bind the same motif and repress transcription. The authors therefore propose a two-stage model for EGA – whereby LEUTX-mediated induction followed by DPRX-mediated repression leads to transient expression of key EGA genes.

Polycomb: promoting stem cell differentiation in the germline

The Drosophila ovary is a valuable model for the investigation of niche-stem cell interactions. In this model, BMP (Dpp) signals from the niche cap cells inhibit differentiation of germline stem cells (GSCs), at least partially through repression of the transcription factor bam. Away from the niche, germline cells are in contact with somatic escort cells, which support GSC differentiation and do not express dpp. Several mechanisms have been uncovered that contribute to the regulation of dpp expression and signal transduction, and on p. 3449, Rongwen Xi and co-workers reveal an important role for Polycomb group (PcG)-mediated modulation of dpp. Depletion of Polycomb repressive complex 1 (PRC1) components in escort cells causes aberrant expression of dpp, leading to tumour-like accumulation of GSCs and differentiation failure. This non-autonomous phenotype could be rescued by expression ofbam in the GSCs. PcG usually acts in antagonism to Trithorax group (TrxG) complexes, and the authors further show that knockdown of the TrxG component brm reverses the PcG-depletion phenotype, so GSCs can once again differentiate. Unlike many other cases of PcG-TrxG antagonism, however, brmknockdown or overexpression alone has no effect, suggesting that PcG-mediated dpp repression may be the default state in escort cells. This work adds to our understanding of the mechanisms underlying niche-stem cell interactions and GSC differentiation, and underlines the importance of dynamic chromatin regulation.

PLUS:

Blood stem cells: from beginning to end

In June 2016, scientists from all over the world gathered at EMBL headquarters in Heidelberg, Germany to discuss the recent advances in hematopoietic stem cell research. In their Meeting Review, Anna Bigas and Claudia Waskow summarize the exciting work that was presented and the main themes that emerged from the meeting.

Making sense out of spinal cord somatosensory development

Research over the past couple of decades has identified transcription factor networks that define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally-defined populations with their roles in somatosensory circuits. In their Review, Helen Lai, Rebecca Seal and Jane Johnson review how neuronal diversity in the dorsal spinal cord is generated and discuss the logic underlying how these neurons form the basis of somatosensory circuits.

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