title: Shox2 is required for the proper development of the facial motor nucleus and the establishment of the facial nerves.
abstract: BACKGROUND
  Axons from the visceral motor neurons (vMNs) project from nuclei in the hindbrain to innervate autonomic ganglia and branchial arch-derived muscles. Although much is known about the events that govern specification of somatic motor neurons, the genetic pathways responsible for the development of vMNs are less well characterized. We know that vMNs, like all motor neurons, depend on sonic hedgehog signaling for their generation. Similarly, the paired-like homeobox 2b (Phox2b) gene, which is expressed in both proliferating progenitors and post-mitotic motor neurons, is essential for the development of vMNs. Given that our previous study identified a novel role for the short stature homeobox 2 (Shox2) gene in the hindbrain, and since SHOX2 has been shown to regulate transcription of islet 1 (Isl1), an important regulator of vMN development, we sought to determine whether Shox2 is required for the proper development of the facial motor nucleus.
  
  
  RESULTS
  Using a Nestin-Cre driver, we show that elimination of Shox2 throughout the brain results in elevated cell death in the facial motor nucleus at embryonic day 12.5 (E12.5) and E14.5, which correlates with impaired axonal projection properties of vMNs. We also observed changes in the spatial expression of the vMN cell fate factors Isl1 and Phox2b, and concomitant defects in Shh and Ptch1 expression in Shox2 mutants. Furthermore, we demonstrate that elimination of Shox2 results in the loss of dorsomedial and ventromedial subnuclei by postnatal day 0 (P0), which may explain the changes in physical activity and impaired feeding/nursing behavior in Shox2 mutants.
  
  
  CONCLUSIONS
  Combined, our data show that Shox2 is required for development of the facial motor nucleus and its associated facial (VII) nerves, and serves as a new molecular tool to probe the genetic programs of this understudied hindbrain region.
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive N.W., BI286D, Calgary, AB, T2N 1N4, Canada. jmrosin2013@gmail.com.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Rosin
authors.affiliation: Department of Medical Genetics, Alberta Children's Hospital Research Institute, University of Calgary, 3330 Hospital Drive N.W., Room HS2275, Calgary, AB, T2N 4N1, Canada. kurrasch@ucalgary.ca.
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Kurrasch
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive N.W., BI286D, Calgary, AB, T2N 1N4, Canada. jacobb@ucalgary.ca.
authors.forename: John
authors.initials: J
authors.lastname: Cobb
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology; D005154:Facial Nerve / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D065828:Facial Nucleus / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D005247:Feeding Behavior / Q000502:physiology; D053823:Hedgehog Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007382:Intermediate Filaments / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C109220:NBPhox protein; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C465570:Shh protein, mouse; C484663:Shox2 protein, mouse; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1