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.
Group of Moises Mallo wins Melo e Castro Prize
The group of Moises Mallo at the Instituto Gulbenkian de Ciência was awarded the 2014 Melo e Castro Prize (200.000 euro) of Santa Casa da Misericórdia de Lisboa (SCML) for the project "Improving cell substrates for spinal regeneration therapies". The goal of the Melo e Castro Prize is to promote the development of new responses in the recovery and treatment of vertebral-spinal cord injuries, and ultimately contribute for the improvement of the life quality of patients. For more information, see here.
N-Cadherin Locks Left-Right Asymmetry
The group of Leonor Saúde publish in Developmental Cell: In chicken embryos, molecular asymmetries at Hensen’s node are created by leftward cell movements that occur transiently. We show that N-cadherin can prevent cells to continue indefinitely this movement, thus maintaining the already established asymmetries. We also show that when N-cadherin function is blocked the expression pattern of fgf8 and nodal in the node changes, leading to an altered asymmetry in the Lateral Plate Mesoderm. These findings indicate that asymmetric N-cadherin in the node locks the leftward cell movement and left-right asymmetry. See article here.
The team of Susana Lopes publishes in Developmental Cell
Susana Lopes’ team discovered that the pattern of fluid dynamics observed in the Kupffer’s vesicle, the left-right organizer of the zebrafish embryo, can be used to predict if the position of the internal organs, such as the heart or liver, will be correctly placed or not. They found that the left-right organizer in zebrafish requires the functional motility of at least 30 cilia, with some clustering in the anterior region, for the correct establishment of laterality of the internal organs. See the article on the Dev Cell website.