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Feeding and breathing are essential motor functions and rely on the activity of hypoglossal and phrenic motor neurons that innervate the tongue and diaphragm, respectively. Little is known about the genetic programs that control the development of these neuronal subtypes. The transcription factor Tshz1 is strongly and persistently expressed in developing hypoglossal and phrenic motor neurons. We used conditional mutation of Tshz1 in the progenitor zone of motor neurons ( Tshz1 MN   Δ ) to show that Tshz1 is essential for survival and function of hypoglossal and phrenic motor neurons. Hypoglossal and phrenic motor neurons are born in correct numbers, but many die between embryonic day 13.5 and 14.5 in Tshz1 MN   Δ mutant mice. In addition, innervation and electrophysiological properties of phrenic and hypoglossal motor neurons are altered. Severe feeding and breathing problems accompany this developmental deficit. Although motor neuron survival can be rescued by elimination of the pro-apoptotic factor Bax , innervation, feeding and breathing defects persist in Bax -/- ; Tshz1 MN   Δ mutants. We conclude that Tshz1 is an essential transcription factor for the development and physiological function of phrenic and hypoglossal motor neurons.

Teashirt1 (Tshz1) is essential for the development, survival and function of hypoglossal and phrenic motor neurons