Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations in MECP2, which encodes the transcriptional regulator methyl-CpG-binding protein 2. Its core symptoms include problems with breathing control, which are most severe during wakefulness and are further exacerbated by behavioural arousal. Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to be involved in the aetiology of respiratory dysfunction in RTT. Now, Katz et al. report that acute administration of LM22A-4, a partial BDNF mimetic, completely reverses spontaneous apnoeas (atypical breathing pauses) and respiratory dysregulation during behavioural arousal in Mecp2 mutant mice, an RTT model. Moreover, patch-clamp recordings in Mecp2-null brainstem slices indicate that LM22A-4 decreases synaptic hyperexcitability within specific cell groups in the brainstem’s respiratory network. These findings support the hypothesis that reduced BNDF signalling and respiratory dysfunction in RTT are linked and demonstrate the feasibility of improving neurological function in RTT by redressing imbalances in synaptic excitability. Page 1047
DMM Journal Meeting 2023: Infectious Diseases Through an Evolutionary Lens
The abstract submission deadline for our 2023 Journal Meeting ‘Infectious Diseases Through an Evolutionary Lens’ is 14 July 2023. Find out more and register here.
The Forest of Biologists
The Forest of Biologists is a biodiversity initiative created by The Company of Biologists, with support from the Woodland Trust. For every Research and Review article published in Disease Models & Mechanisms a native tree is planted in a UK forest. In addition to this we are protecting and restoring ancient woodland and are dedicating these trees to our peer reviewers. Visit our virtual forest to learn more.
Propose a new Workshop for 2025
Do you have an idea for a Workshop? If so, click here. We are now accepting proposals for our 2025 Workshops programme. As the scientific organiser, your involvement will be focused on the science. We'll take care of all the logistics. In 2025 we'll continue our efforts to diversify our Workshop programme and will be reserving one of our Workshops for an application from a Global South country to host an event overseas.
How stromal cells restrict liver cancer invasion
In our recent editor’s choice, Liqin Zhu and colleagues describe how they used in vitro liver spheroid models consisting of both parenchymal and non-parenchymal cells to reveal a hepatoprotective role for peritumoral hepatic stellate cells in liver tumorigenesis.
And from perspective… Hacking haematopoiesis – emerging tools for examining variant effects
Thousands of genomic loci have been linked to hematopoietic traits and diseases, yet many await functional validation. Michael Gundry and Vijay G. Sankaran discuss recent advances in genome editing and the challenges associated with using these techniques to assess variant function in primary hematopoietic cells. a celebration of the achievements of female scientists, and a call to action for a culture shift in science.
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