MN development is a multi-step process that takes place both prior to, and following, acquisition of post-mitotic neuronal features. Despite their vital biological role, little is presently known about the mechanisms controlling the diversification of hypaxial respiratory MNs during spinal cord development. Thus, selective death of hypaxial MNs and their defective function in disease cause devastating ventilatory insufficiencies 7. Although most breathing functions are controlled by phrenic MNs and the diaphragm in human, a quarter of respiration depends primarily on hypaxial MNs capacity to contract intercostal muscles, allowing the thoracic cavity and the lungs to expand and deflate. Axial muscle-innervating motor neurons (MNs) are usually found along the entire spinal cord length, whereas phrenic and hypaxial muscle-innervating MNs in mammals, are segmentally restricted to cervical and thoracic levels 3- 6. As a result, vertebrates from birds to mammals share the feature of using axial muscles to maintain their stance while hypaxial muscles assist breathing 1, 2.

These findings provide evidence for essential and sequential roles of TLE in the spatial and temporal coordination of events regulating the development of motor neurons influencing posture and controlling respiration.Īxial and hypaxial muscles, which control undulatory locomotor behaviour in primitive chordates, have evolved in more complex organisms to sustain erectile body posture or control vital functions such as respiration. TLE further acts during post-mitotic motor neuron diversification to promote axial motor neuron topology and axonal connectivity whilst suppressing hypaxial traits. TLE first promotes axial motor neuron specification at the expense of hypaxial identity by cooperating with non-canonical WNT5A signalling within the motor neuron progenitor domain.

Here we show that the Groucho/TLE (TLE) transcriptional corepressor is a multi-step regulator of axial and hypaxial motor neuron diversification in the developing spinal cord. Little is known, however, about the molecular mechanisms behind the specification of axial and hypaxial motor neurons controlling postural and respiratory functions respectively. Spinal cord motor neuron diversity and the ensuing variety of motor circuits allow for the processing of elaborate muscular behaviours such as body posture and breathing.

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