In Development this week (Vol. 144, Issue 8)

Here are the highlights from the current issue of Development:

A new niche for human HSCs

Human haematopoiesis occurs at various anatomical sites throughout development, including the yolk sac, the aorta-gonad-mesonephros region, the liver, the placenta and the bone marrow. Cells marked by high expression of CD34 and low CD45 – suggestive of possible HSCs – have been reported in human fetal membranes; however, their exact niche as well as their functional capacity remain untested. In this issue (p. 1399), Alicia Bárcena and colleagues isolate and interrogate this putative HSC population, and demonstrate for the first time that the human chorion contains transplantable, definitive HSCs. The authors carefully separate the chorion and the amnion, and show via fluorescence-activated cell sorting that only the chorion contains the putative HSCs, and only from 15 weeks of gestation. The cells display markers of HSC and primitive haematopoietic progenitors, such as little CD38 and CD133, low levels of CD117 and CD4, and medium to high levels of HLA-DR, CD31, CD90, CD95, TIE2 and CD71. Cells co-expressing CD34 and CD45 antigens are found either in association with mesenchymal stromal cells or with endothelial cells of chorion vasculature . Using in vivo xenotransplantations, the authors demonstrated that the CD34⁺⁺ CD45^low cells possess multilineage long-term HSC activity specifically between weeks 15 and 24 of gestation. This study reveals novel insight into an unexpected niche for HSCs during human development.

How the stomach gets its curve

Left-right asymmetry is a common feature of many organs, and is crucial for their function. The stomach is one such organ, with marked curvature on the left compared with the right, resulting in a distinctive shape that is highly conserved among vertebrates. Although it is well established that activation of Nodal controls left-right asymmetry of visceral organs, the cell- and tissue-level morphogenetic mechanisms that drive this phenomenon are poorly understood, especially in the stomach. Now, on p. 1477, Nanette Nascone-Yoder and colleagues shed light on the mechanisms that drive left-right asymmetric development of the stomach in both mouse and Xenopus embryos. The authors start with a gross examination of stomach curvature during development and compare their findings with two proposed models: a rotation model and an asymmetric growth model. They find no evidence for the former, and therefore suggest that the stomach acquires its asymmetry by an intrinsic mechanism. In support of this, the authors show that there is an asymmetric thickness of the left and right stomach wall, which depends on intact cilia and Nodal signalling as both Foxj1 mutant mouse embryos and Xenopus embryos treated with a Nodal inhibitor show a loss of this asymmetry. The authors show a role for Pitx2 in this process by overexpressing Pitx2 on the right side or knocking down Pitx2, both of which affect stomach curvature in Xenopus. This study demonstrates that asymmetric morphogenesis of the stomach in frogs and mice is driven by FoxJ1-Nodal-Pitx2-dependent asymmetric remodelling of the gastric epithelium on the left side.

Liverworts breathe easy

The vast majority of land plants regulate gas exchange through their stomata – tiny pores usually found on the underside of leaves. The liverwort plant group Marchantiidae is an exception, as it lacks stomata and instead breathes through air pore complexes. This is an important evolutionary adaptation, and yet the mechanisms that regulate air pore complex development in Marchantiidae remain unknown. In this issue (p. 1472), Victor Jones and Liam Dolan identify the zinc finger protein MpWIP as necessary for the morphogenesis of the air pore complex in the epidermis of Marchantia polymorpha. The gene was first identified through a mutagenesis screen, in which overexpression led to the presence of ectopic rhizoids on the dorsal epidermis. Using a construct containing the MpWIP promoter fused to a reporter gene, the authors show that MpWIP is expressed both ventrally and dorsally and that the dorsal expression pattern is within the developing air pore complex cells. To determine whether MpWIP is required for air pore development, the authors use artificial microRNAs to generate plants with reduced expression of MpWIP, which results in defects in air pore complex morphology. Based on chimeric dominant repressor and activator versions of MpWIP expressed separately in transgenic plants, the authors provide some evidence for the possible role of MpWIP as a transcriptional repressor. This study identifies, for the first time, a gene that regulates the development of the air pore complex, which is an important evolutionary innovation in liverworts as an alternative to stomata.

Specialised fibroblasts maintain the nipple epidermis

The skin is the body’s largest organ, and is the first line of defence against the external environment. The epidermis – the outermost layer of the skin – is highly specialised and often exhibits unique characteristics depending on its anatomical location and the function it serves. It has long been known that this specialisation is dependent on inductive signals that originate from underlying fibroblasts; however, the exact nature of the signals and their role in maintaining the epidermis is only just starting to emerge. In this issue (p. 1498), John Foley and colleagues identify an oestrogen-regulated TGFβ signalling pathway that is crucial for the maintenance of the highly specialised nipple epidermis. Using a series of grafting experiments, the authors show that fibroblasts taken from the nipple-like skin of mice can induce reprogramming of trunk keratinocytes into nipple-like epidermis. Transcriptional profiling of the nipple-like fibroblasts identifies oestrogen signalling as a strong candidate factor for the maintenance of the nipple epidermis and, indeed, ablation of oestrogen signalling in ovariectomised mice results in an abnormally thin nipple epidermis. The authors further identify Tgfb1 as a direct target of oestrogen signalling and show how ectopic treatment of TGFβ1 protein into the connective tissue of the nipple causes a decrease in epidermal proliferation and a thinning of the nipple epidermis. Taken together, these data represent an important step forward in understanding the signalling network that maintains the specialisation of the nipple epidermis.

PLUS:

Stem cell therapies for retinal diseases: recapitulating development to replace degenerated cells

Retinal degenerative diseases are the leading causes of blindness worldwide. In their Review article, Sally Temple and colleagues review stem cell-based therapies for retinal diseases, describing the challenges involved and discussing how basic developmental studies have contributed to and are needed to advance clinical goals.

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

Prostate organogenesis is a complex process that is regulated by androgens and subsequent mesenchyme-epithelial interactions. In their Review article, Roxanne Toivanen and Michael Shen provide a comprehensive overview of prostate development, focusing on recent findings regarding sexual dimorphism, bud induction, branching morphogenesis and cellular differentiation.

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