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In Development this week (Vol. 142, Issue 6)

Posted by , on 10 March 2015

Here are the highlights from the current issue of Development:


Dmrt1: a common thread in sex determination

FigureDmrt1 and its related genes play a key role in sex determination in a broad range of metazoan species. However, Dmrt1 has become dispensable for testis determination in mammals, and this function is instead carried out by Sry, which is a newly evolved gene found on the Y chromosome. Now, Peter Koopman and colleagues show that, even though its function is not normally required, Dmrt1 is able to drive female-to-male sex reversal in mice (p. 1083). The researchers show that the transgenic overexpression of Dmrt1 in XX mouse foetal gonads is able to induce testis formation. The resulting gonads exhibit typical testicular size and vascular patterning, and contain Sertoli cells that express the hallmark testis-determining gene Sox9. By contrast, the expression of ovarian markers is repressed and granulosa cells are absent. The researchers further show that this testis phenotype persists into adulthood; male internal and external reproductive organs develop, whereas female structures are absent. Together, these findings suggest that Dmrt1 has retained the ability to act as a sex-determining factor in mammals, highlighting a common thread in the evolution of sex-determination mechanisms in metazoans.


Uncovering feedback in plant stem cell networks

FigureIn plants, stem cell proliferation is negatively regulated by the receptor kinase CLAVATA1 (CLV1) and its peptide ligand CLAVATA3 (CLV3). Previous studies have suggested that CLV1 acts redundantly with other receptor kinases, such as BAM1, 2 and 3, but the molecular mechanisms underpinning this redundancy have been unclear. Now, Elliot Meyerowitz and co-workers interrogate the role of CLV1-CLV3 signalling in the Arabidopsis shoot apical meristem (p. 1043). They first show that CLV1 functions exclusively in rib meristem (RM) cells that express the transcription factor WUSCHEL, which is required for stem cell maintenance. The researchers further show that BAM1 and BAM3 expression is absent in these CLV1-expressing cells, suggesting that CLV1 represses BAM1/3 expression. In line with this, they reveal that BAM1 and BAM3 are transcriptional targets of the CLV1-CLV3 signalling pathway. Finally, they report that CLV1 in the RM is necessary and sufficient for the negative regulation of stem cell proliferation, independent of BAM function; the apparent genetic redundancy observed is due to the ectopic expression of BAM genes in the absence of CLV1-CLV3 signalling. Together, these findings clarify the role of CLV1-CLV3 signalling and uncover a novel feedback loop that operates in the plant stem cell niche.


Gata2b: an early regulator of HSC emergence

FigureHematopoietic stem cells (HSCs) give rise to all cells of the adult blood system, and understanding how these cells first arise during embryogenesis is important for developing regenerative medicine-based strategies for producing HSCs in vitro. Here, David Traver and colleagues demonstrate that Gata2b acts as an early regulator of zebrafish hematopoietic precursors (p.1050). The zebrafish genome contains two Gata2orthologues – gata2a and gata2b – and the researchers show that gata2b is expressed in a distinct subpopulation of endothelial cells within the dorsal aorta (DA), which gives rise to HSCs; gata2a in contrast is expressed throughout the DA. This expression of gata2b is Notch-dependent and occurs prior to the expression of runx1, which to date has served as an early marker of zebrafish HSCs. Using lineage tracing, the researchers further show that gata2b-expressing cells give rise to adult HSCs. Finally, knockdown studies indicate that gata2b is required for the formation of functional HSCs. In summary, this study reveals that Gata2b functions as an early marker and regulator of HSCs, prompting further studies into the role of Gata2 during HSC emergence.


Magi keeps an eye on AJ remodelling

FigureAdherens junctions (AJs), which are specialised E-cadherin-based cell contacts, are continuously remodelled during tissue morphogenesis, as cells change shape and position. The accumulation of Bazooka (Baz), the Drosophila PAR3 homologue, is thought to specify where new E-cadherin complexes are deposited during AJ remodelling, but what regulates Baz localisation? Here, Alexandre Djiane and colleagues show that the scaffold protein Magi regulates Baz localization and hence AJ remodelling inDrosophila eye epithelial cells (p. 1102). By studyingMagi mutants, the researchers first show that Magi is required for the correct sorting of interommatidial cells during pupal eye development. They further show that Magi directly interacts with the Ras association domain protein RASSF8. This interaction, they report, is mediated by a WW domain-PPxY binding motif and is required for Magi function in the fly eye. They further demonstrate that Magi recruits a RASSF8-ASPP complex to AJs and that this, in turn, is required for the cortical recruitment of Baz to AJs during junctional remodelling. Overall, these findings highlight the importance of this novel Magi-RASSF8-ASPP complex for AJ remodelling and tissue morphogenesis.




Skeletal stem cells

DEV1023Skeletal stem cells (SSCs) reside in the postnatal bone marrow and give rise to cartilage, bone, hematopoiesis-supportive stroma and marrow adipocytes. Here, Paolo Bianco and Pamela Robey discuss the biology of SSCs in the context of the development and postnatal physiology of skeletal lineages, to which their use in medicine must remain anchored. See the Development at a Glance poster article on p. 1023


Mammary gland development

DEV1028The mammary gland provides an excellent model for studying ‘stem/progenitor’ cells, which – in this context – allow for the repeated expansion and renewal of the gland  during adult life. Here, Mina Bissell and colleagues discuss the various cell types that constitute the mammary gland, highlighting how they arise and differentiate, and how the microenvironment influences their development. See the Review on p. 1028

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