Development of the mesencephalic trigeminal nucleus requires a paired homeodomain transcription factor, Drg11

Abstract

The mesencephalic trigeminal nucleus (Me5) innervates muscle spindles and is responsible for receiving and transmitting proprioception from the oro-facial region. Molecular mechanisms underlying the development of the Me5 are poorly understood. Evidence is provided here that transcription factor Drg11 is required for Me5 development. Drg11 was expressed in the Me5 cells of the embryonic and early postnatal mouse brains, and the Me5 cells were absent in Drg11 −/− mice at birth. The absence of the Me5 cells in Drg11 −/− mice appeared to be caused by increased cell death in the Me5 during embryonic development. In postnatal Drg11 −/− mice, Me5 cell innervation of masseter muscle spindles was undetectable, while robust trigeminal motoneuron innervation of masseter muscle fibers was detected. The postnatal bodyweight of Drg11 −/− mice was notably less than that of wild-type mice, and this might result, in part, from disruption of the oro-facial proprioceptive afferent pathway. Taken together, our results demonstrate an essential role for Drg11 in the development of the Me5.

InDRG11Knock-Out Mice, Trigeminal Cell Death Is Extensive and Does Not Account for Failed Brainstem Patterning

“…However, the expression of DRG11 in the entire size range of V ganglion cells and mesencephalic V proprioceptors, along with its expression in the PrV (but not the SpVi), which exclusively receives large-caliber mechanoreceptor inputs (Shortland et al, 1996), suggest additional DRG11 functions in the V system beyond sustaining small ganglion cells. Data presented here and previously (Ding et al, 2003;Wang et al, 2007) suggest that DRG11 is necessary for the survival of V mesencephalic proprioceptors and that DRG11 has an indispensable function in whisker-related pattern formation in the PrV by some mechanism other than ensuring neuronal survival.…”

“…Previous studies (Chen et al, 2001;Ding et al, 2003;Wang et al, 2007) indicate that the mouse DRG11 gene is expressed in the developing spinal dorsal root ganglia and dorsal horn, V ganglion, mesencephalic V nucleus, and PrV. There is a suggestion (Rebelo et al, 2006) that DRG11 selectively sustains "small" dorsal root ganglion cells that tend to be nociceptors, consistent with its expression in the superficial dorsal horn (Chen et al, 2001).…”

Abolition of lemniscal barrellette patterning in Prrxl1 knockout mice: Effects upon ingestive behavior

“…Prrxl1 (previously named DRG11) is required for patterning of nociceptive circuitry in the dorsal spinal cord (Saito et al 1995;Chen et al 2001). Its deletion also disrupts the normal development of patterning in the lemniscal system, abolishing whiskerrelated barrellettes in the lemniscal brainstem nucleus (PrV) while leaving them intact in the paralemniscal brainstem nucleus (SpVi) (Wang et al 2007;Jacquin et al 2008). Thus Prrxl1 deletion, by disrupting pattern formation in the lemniscal, but not the paralemniscal trigeminal pathway, provides an opportunity to dissociate the functions of the two pathways in trigeminally mediated behaviors.…”

Critical care and survival of fragile animals: The case of Prrxl1 knockout mice

“…Only two previous studies were able to maintain animals until adulthood, and even on those cases they were a few animals and younger than 6 months (Chen et al, 2001;Wang et al, 2007). Importantly, one of these studies (Wang et al, 2007) suggested that the loss of proprioceptive afferent input from masticatory muscles could be responsible for difficulties in feeding behaviour in Prrxl1 −/− mice.…”

“…Importantly, one of these studies (Wang et al, 2007) suggested that the loss of proprioceptive afferent input from masticatory muscles could be responsible for difficulties in feeding behaviour in Prrxl1 −/− mice. Since Prrxl1 −/− animals are smaller than heterozygous and wildtype mice, we hypothesized that early lethality could be due to insufficient feeding.…”