Dilp8–Lgr3 critical to ensure developmental stability in Drosophila

The group of Alisson Gontijo at CEDOC discovered a novel neuroendocrine circuit responsive to growth aberrations. Different organs need to sense growth perturbations in distant tissues to coordinate their size and differentiation status during development. The Gontijo team determined that the sensing of peripheral growth perturbations in the fruit fly (Drosophila melanogaster) requires a novel population of CNS neurons expressing the Lgr3 relaxin receptor. Neuronal Lgr3 is required for the transmission of the peripheral growth aberration signal, Dilp8, to the prothoracic gland, which controls the onset of metamorphosis and thereby the cessation of imaginal disc growth. This work reveals a new Dilp8–Lgr3 pathway that is critical to ensure developmental stability in Drosophila. See the paper here.

aECM to F-actin feedback mechanism

Sofia Araújo and collaborators discovered an apical ECM to F-actin feedback mechanisms in tracheal cells which was recently published in eLife. The authors show that there is an active feedback mechanism between apical ECM (aECM) and the apical F-actin in tracheal cells. Cell-cell junctions are shown to be key players in this aECM patterning and organisation and that individual cells contribute autonomously to their aECM. Strikingly, changes in the aECM influence the levels of phosphorylated Src42A (pSrc) at cell junctions. The authors propose that Src42A phosphorylation levels provide a link for the extracellular matrix environment to ensure proper cytoskeletal organisation. See paper here.

Hoxb6 can interfere with the segmentation program

The group of Moises Mallo at the Instituto Gulbenkian de Ciência published in Development. The authors show that forced expression of Hoxb6 in the paraxial mesoderm produces non-rib-related malformations due to problems in somitogenesis and anterior-posterior somite patterning, which result from dysregulated expression of the oscillator gene Lfng. Dysregulated Lfng expression was restricted to regions posterior to the hindlimb, suggesting that the mechanisms of paraxial segmentation are not uniform along the main body axis as previously thought. These data provide a mechanistic connection between Hoxb6 expression and the mammalian segmentation clock and convincingly demonstrate functional differences in somitogenesis before and after the trunk-to-tail transition. The authors postulate that their data suggest the existence of yet-to-be-identified differential mechanisms operating during development of the trunk or tail areas of the body axis. See article here.

Simple recipe to make sensory hair cells in the ear

The group of Domingos Henrique, at the Molecular Medicine Institute in Lisbon, in collaboration with the University College London Ear Institute, have developed a simple and efficient protocol to generate inner ear hair cells, the cells responsible for our hearing and sense of balance. This study is an important step for the future production of large numbers of these cells for use in cell transplantation therapies or large scale drug screens. The research has just been published in the scientific journal Development. See article here.

Sensory hair cells located in the inner ear are vital for our sense of hearing and balance. As these cells are unable to regenerate, millions of people worldwide have permanent hearing and balance impairments.  Previous studies had already reported the successful generation of hair cells in the lab, but the protocols were complex and inefficient. To get around these problems, the team led by Domingos Henrique, whose Neural Development lab is also associated with the Champalimaud Centre for the Unknown in Lisbon, decided to follow a different strategy. ‘We explored the extensive knowledge on the various regulatory proteins that control hair cell development in the embryo to design an effective combination of three transcription factors able to induce the formation of these cells’, said Dr Henrique and Aida Costa, the graduate student involved in the work.

The team applied this simpler approach to mouse embryonic stem cells in a dish, which have the potential to become any cell type. They were able to convert these cells into hair cells, more successfully and with higher efficiencies than previously reported. Excitingly, when the team added the three players to cells in the ear of a developing chick embryo they were also able to induce the formation of many new hair cells, including in areas where they do not normally form, suggesting that a similar strategy might work in vivo.

‘Hair cells get their name from the bundle of hair-like structures that protrude from the cell. These protrusions have mechanosensitive ion channels that allow hair cells to transform vibrational movements into electrical signals. We observed that the hair cells we produced are also able to develop similar protrusions, but with an immature and disorganized morphology’, said the authors. ‘However, we have some evidence suggesting that functional mechanosensitive ion channels are already present in these cells, and that the genes expressed by normal hair cells and those produced by us in a dish are very similar.’

Future work will focus both on improving this protocol to produce fully mature hair cells, and on applying the method to human cells that can be produced in large quantities. ‘Producing large numbers of hair cells will allow the development of high-throughput drug screening to discover new compounds that can promote hair cell regeneration. In the long-term, they can also be used as a starting-point to develop cell-replacement therapies that could successfully restore the lost or damaged hair cells in the inner ear’, concluded the authors.