Formation of whisker-related principal sensory nucleus-based lemniscal pathway requires a paired homeodomain transcription factor, Drg11.
Little is known about the molecular mechanisms underlying the formation of the principal sensory nucleus (PrV) of the trigeminal nerve, a major relay station for somatotopic pattern formation in the trigeminal system. Here, we show that mice lacking Drg11, a homeodomain transcription factor, exhibit defects within the PrV, which include an aberrant distribution of Drg11-/- cells, altered expression of a molecular marker, unusual projections of primary afferents from trigeminal ganglion cells, and, subsequently, increased cell death. In addition, surviving PrV cells exhibit delayed and more spatially restricted ascending projections to the ventral posterior medial nucleus of the thalamus (VPm). These early embryonic abnormalities in the PrV lead to the failure to develop whisker-related patterns in the PrV, VPm, and somatosensory cortex. By contrast, somatotopic patterns exist in the spinal trigeminal subnuclei interpolaris (SpVi) and subnuclei caudalis (SpVc) and the dorsal column nucleus-based lemniscal and cortical pathway. Thus, the deficits in the trigeminal system of Drg11-/- mice are specific to the PrV. Our results demonstrate that Drg11 is essential for proper cellular differentiation and, subsequently, for the formation of the whisker-related lemniscal and cortical structures.
Ding
Yu-Qiang
YQ
Department of Anesthesiology, School of Medicine, Washington University, St. Louis, Missouri 63110, USA.
Yin
Jun
J
Xu
Hai-Ming
HM
Jacquin
Mark F
MF
Chen
Zhou-Feng
ZF
D000344:Afferent Pathways; D000818:Animals; D016923:Cell Death; D004268:DNA-Binding Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000032:analysis; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D013788:Thalamus / Q000166:cytology / Q000196:embryology; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology; D014278:Trigeminal Nuclei / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D014738:Vibrissae / Q000294:innervation*
D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C433766:Prrxl1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D003576:Electron Transport Complex IV