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In Development this week (Vol. 143, Issue 13)

Posted by , on 5 July 2016

Here are the highlights from the current issue of Development:

 

A pioneer role for PBX1 in neurogenesis

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The adult rodent subventricular zone (SVZ) is a neurogenic niche that provides new neurons and glia to the brain. A number of transcription factors, including MEIS2 and PAX6, are known to be required to promote the neuronal cell fate. PBX family proteins can interact with both MEIS and PAX family factors, and PBX1 is known to be expressed in the adult mouse forebrain. Dorothea Schulte and colleagues therefore set out to test the role of PBX1 in SVZ neurogenesis (p. 2281). They show that Pbx1expression is found in rapidly proliferating SVZ progenitors, as well as in subsets of their progeny in the olfactory bulb. Its ortholog, PBX2, is more widely expressed in the forebrain. Deletion of both genes in the adult SVZ leads to a reduction in neurogenesis and a concomitant increase in oligodendrogliogenesis – an alternative fate for SVZ progenitors. Although the authors can detect PBX1 binding to MEIS2 and PAX6, the phenotype is distinct from functional blockade of these factors, suggesting an at least partially independent function. Intriguingly, PBX1 appears to bind its targets before they are transcriptionally activated, indicating a putative pioneer factor function for PBX1. These data identify PBX1 as an important new regulator of SVZ neurogenesis.

 

A tyrosine kinase for FERtilisation

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Mammalian sperm need to undergo capacitation to become competent to fertilise the oocyte. In vivo, this occurs in the female reproductive tract, whereas in vitro it can be triggered by culture in defined media. One of the key events during capacitation is cAMP-dependent tyrosine phosphorylation of various proteins. Although this phenomenon has been well described in many species, the kinase responsible has been elusive. Various candidates have been proposed, including SRC, FAK and PYK2; notably, inhibitors for the latter two enzymes block tyrosine phosphorylation in human and horse sperm. However, definitive evidence for the identity of the kinase has been lacking. Now (p. 2325), Pablo Visconti and co-workers show that, while FAK and PYK2 inhibitors also block tyrosine phosphorylation in mouse sperm (without blocking PKA activation), neither is the responsible factor. Instead, it is the FER kinase – also targeted by the same inhibitors – that carries out capacitation-associated tyrosine phosphorylation. However, and surprisingly, FER is not required for fertilisation in vivo, suggesting that the presumed involvement of tyrosine phosphorylation in acquisition of sperm competence may need to be revisited.

 

Coordinating morphogenesis and differentiation with WNT

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The mammalian salivary gland is a valuable model for analysis of the morphogenetic and differentiation events that occur during branching morphogenesis of organs. Following a period of growth and branching, epithelial cells of the salivary gland differentiate down ductal or acinar routes. What are the signalling mechanisms that control morphogenesis, differentiation and lineage choice, and how are these processes coordinated to ensure appropriate size and composition of the final organ? The FGF pathway is known to play key roles in salivary gland development, including via the activation of KIT signalling – which promotes the expansion of distal (future acinar) progenitors. Moreover, WNT signalling has been implicated in salivary gland morphogenesis, although its function is unclear. On p.2311, Akira Kikuchi and colleagues use genetic and pharmacological approaches, both in vivo and in vitro, to demonstrate that mesenchymally derived WNT signals inhibit acinar differentiation and maintain end bud cells in an undifferentiated state, to promote secondary and tertiary duct formation. Mechanistically, WNT activity promotes MYB-dependent inhibition of Kit expression; KIT directs acinar differentiation through AKT. As WNT pathway activity is dynamically regulated, the authors propose this as a means by which salivary gland morphogenesis and differentiation can be spatiotemporally coordinated.

 

PLUS!

 

Cell behaviors and dynamics during angiogenesis

Fig 5cell behaviors horizontal_revised_Apr2016-CBVascular networks are formed and maintained through a multitude of angiogenic processes, such as sprouting, anastomosis and pruning. Only recently has it become possible to study the behavior of the endothelial cells that contribute to these networks at a single-cell level in vivo. Here, Markus Affolter and colleagues summarizes what is known about endothelial cell behavior during developmental angiogenesis, focusing on the morphogenetic changes that these cells undergo. See the Review on. p. 2249.

 

Generation of intestinal surface: an absorbing tale

Villi review GumicoThe vertebrate small intestine requires an enormous surface area to effectively absorb nutrients from food. Morphological adaptations required to establish this extensive surface include generation of an extremely long tube and convolution of the absorptive surface of the tube into villi and microvilli. In their Review, Deborah Gumucio and colleagues discuss recent findings regarding the morphogenetic and molecular processes required for intestinal tube elongation and surface convolution in different species. See the Review on p. 2261.

 

Dental mesenchymal stem cells

Tooth 1 SharpeMammalian teeth harbour mesenchymal stem cells (MSCs), which contribute to tooth growth and repair. These dental MSCs possess many in vitro features of bone marrow-derived MSCs, including clonogenicity, expression of certain markers, and following stimulation, differentiation into cells that have the characteristics of osteoblasts, chondrocytes and adipocytes. Here, Paul Sharpe outlines some recent discoveries in dental MSC function and behaviour and discusses how these and other advances are paving the way for the development of new biologically based dental therapies. See the Review on p. 2273.

 

 

 

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