Teashirt 1 (Tshz1) is essential for the development, survival and function of hypoglossal and phrenic motor neurons in mouse.

Charlotte Chaimowicz,Andrew Woehler,Alistair N Garratt,Carmen Birchmeier,Gilles Fortin,Niccolò Zampieri,Cyril Chéret,Pierre-Louis Ruffault

doi:10.1242/dev.174045

Abstract

ABSTRACTFeeding 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 (Tshz1MNΔ) 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 Tshz1MNΔ 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−/−; Tshz1MNΔ mutants. We conclude that Tshz1 is an essential transcription factor for the development and physiological function of phrenic and hypoglossal motor neurons.

Highlights

Breathing and feeding are motor behaviors that are essential for the survival of all terrestrial vertebrates
Analysis of teashirt zinc finger homeobox 1 (Tshz1)-driven GFP expression in the spinal cord and brainstem showed the presence of GFP in several neuronal types, among them motor neurons
Tshz1 expression was spatially restricted to subdomains of the hypoglossal nucleus at P0.5, a finding that became apparent in a 3D reconstruction of the hypoglossal nucleus (Fig. 1C; see Fig. S5 for examples of sections used for the reconstruction)

Summary

Introduction

Breathing and feeding are motor behaviors that are essential for the survival of all terrestrial vertebrates. They rely on complex neuronal networks, including motor neurons that are the ‘executive’ components controlling the activity of specific muscle groups (Moore et al, 2014). The activity of phrenic and hypoglossal motor neurons has to be tightly coordinated to avoid maladaptive outcomes such as the swallowing of air or the blockage of airways (Moore et al, 2014). Hypoglossal and phrenic motor neurons and the circuitry that coordinates their activity are essential for animal survival. Relatively little is known about the formation of the motor neurons that relay breathing and feeding commands

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