Fetal development of the respiratory tract and diaphragm requires strict coordination between genetically controlled signals and mechanical forces produced by the neural network that generates breathing. Being expressed in the mesenchyme of trachea, lung and diaphragm, and in phrenic motoneurons HOXA5 is a key transcription factor regulating lung development and function. Consequently, most Hoxa5−/− mutants die at birth from respiratory failure. However, the extensive effect of the null mutation makes it difficult to identify the origins of respiratory dysfunction in newborns. To address the physiological impact of Hoxa5 tissue-specific roles, we used conditional gene targeting with the Dermo1Cre and Olig2Cre mouse lines to produce specific Hoxa5 deletions in mesenchyme and motoneurons, respectively. Hoxa5 expression in mesenchyme is critical for trachea development, whereas its expression in phrenic motoneurons is essential for diaphragm formation. Breathing measurements in adult mice with whole body plethysmography demonstrated that at rest, only the motoneuron deletion affects respiration due to higher breathing frequency and decreased tidal volume. But subsequent exposure to a moderate hypoxic challenge (FiO2=0.12; 10 min) revealed that both mutant mice hyperventilate more than controls. Hoxa5flox/flox;Dermo1+/cre mice showed augmented tidal volume while Hoxa5flox/flox;Olig2+/cre mice had the largest increase in breathing frequency. No significant differences were observed between medulla-spinal cord preparations from E18.5 control and Hoxa5flox/flox;Olig2+/Cre mouse embryos that could support a role for Hoxa5 in fetal inspiratory motor command. According to our data, Hoxa5 expression in mesenchyme and phrenic motor neurons controls distinct aspects of respiratory development.
Respiratory consequences of targeted losses of Hoxa5 gene function in mice
Both authors contribute equally to this work.
2023 JEB Outstanding Paper Prize shortlist and winner
The JEB Editors are delighted to announce the shortlisted authors for the 2023 JEB Outstanding Paper Prize. Read the winning paper - Tiny spies: mosquito antennae are sensitive sensors for eavesdropping on frog calls - by Hoover Pantoja-Sanchez and Brian Leavell from Ximena Bernal's lab at Purdue University, USA.
JEB Science Communication Workshop for ECRs
If you’re an early-career researcher interested in science communication and are attending the SEB Annual Conference in Prague this summer, come a day early and join the JEB Editors at a sci comm workshop to learn the key writing skills needed to promote your research to a broad audience beyond your peers (1 July at 14.30-17.30). Places are limited to 24 attendees, and applicants should apply through the SEB registration page by 30 April 2024.
Bridging the gap between controlled conditions and natural habitats in understanding behaviour
Novel technologies enable behavioural experiments with non-model species, in naturalistic habitats and with underexplored behaviours. In their Commentary, Scholz and colleagues discuss how to obtain a deeper understanding of the natural ecology and lifestyle of study animals.
Beluga metabolic measures could help save species
To help save animals from extinction, it’s important to understand what each species needs to survive. This led Jason John et al. to measure the metabolic rates of captive belugas to develop a ‘fish calculator’ showing that the whales need to eat ~23 salmon per day.
ECR Workshop on Positive Peer Review
Are you an ECR looking for tips on how to write concise, astute and useful manuscript reviews? If so, join the JEB Editors at a 2-hour JEB-sponsored Workshop on Positive Peer Review at the Canadian Society of Zoologists annual meeting in Moncton on 9 May 2024 at 13.00-15.00. There are 25 spaces for ECRs and selection is first come, first serve. To sign up, check the ECR Workshop box when you register for the CSZ meeting.
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