Abstract
Cranial motor nerves in vertebrates are comprised of the three principal subtypes of branchial, visceral, and somatic motor neurons, which develop in typical patterns along the anteroposterior and dorsoventral axes of hindbrain. Here we demonstrate that the formation of branchial and visceral motor neurons critically depends on the transcription factors Nkx2.2 and Nkx2.9, which together determine the cell fate of neuronal progenitor cells. Disruption of both genes in mouse embryos results in complete loss of the vagal and spinal accessory motor nerves, and partial loss of the facial and glossopharyngeal motor nerves, while the purely somatic hypoglossal and abducens motor nerves are not diminished. Cell lineage analysis in a genetically marked mouse line reveals that alterations of cranial nerves in Nkx2.2; Nkx2.9 double-deficient mouse embryos result from changes of cell fate in neuronal progenitor cells. As a consequence progenitors of branchiovisceral motor neurons in the ventral p3 domain of hindbrain are transformed to somatic motor neurons, which use ventral exit points to send axon trajectories to their targets. Cell fate transformation is limited to the caudal hindbrain, as the trigeminal nerve is not affected in double-mutant embryos suggesting that Nkx2.2 and Nkx2.9 proteins play no role in the development of branchiovisceral motor neurons in hindbrain rostral to rhombomere 4.
Highlights
In vertebrates the cranial motor nerves control the muscles on which eye, head and neck movements, swallowing, sound formation and facial expressions depend
We demonstrate that the neuronal progenitor cell lineage in the p3 domain is transformed to the sMN fate in the absence of both Nkx2.2 and Nkx2.9 factors, even in rhombomeres 4 and 6, which are normally devoid of somatic motor neurons
The spinal accessory nerve was almost completely missing in Nkx2.2/Nkx2.9 double-deficient embryos and the vagal nerve was substantially reduced in size with considerably fewer rootlets (Fig 1)
Summary
In vertebrates the cranial motor nerves control the muscles on which eye, head and neck movements, swallowing, sound formation and facial expressions depend. Cell somata of cranial motor neurons are partitioned into distinct nuclei residing in well-defined areas of the brainstem including midbrain and hindbrain. The vast majority of motor neurons localizes to the hindbrain, which during embryonic development becomes segmented along the rostrocaudal axis. These functionally and molecularly distinct units are referred to as rhombomeres which obtain their individual identity by the expression of a specific combination of Hox genes in the particular segment [1]. Hox gene patterns are controlled, at least in part, by the diffusible signals FGF8 and retinoic acid present in rostral and caudal sections of hindbrain, respectively.
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