Lack of the Central Nervous System- and Neural Crest-Expressed Forkhead Gene Foxs1 Affects Motor Function and Body Weight

Abstract

To gain insight into the expression pattern and functional importance of the forkhead transcription factor Foxs1, we constructed a Foxs1-␤-galactosidase reporter gene "knock-in" (Foxs1 ␤-gal/␤-gal ) mouse, in which the wild-type (wt) Foxs1 allele has been inactivated and replaced by a ␤-galactosidase reporter gene. Staining for ␤-galactosidase activity reveals an expression pattern encompassing neural crest-derived cells, e.g., cranial and dorsal root ganglia as well as several other cell populations in the central nervous system (CNS), most prominently the internal granule layer of cerebellum. Other sites of expression include the lachrymal gland, outer nuclear layer of retina, enteric ganglion neurons, and a subset of thalamic and hypothalamic nuclei. In the CNS, blood vessel-associated smooth muscle cells and pericytes stain positive for Foxs1. Foxs1␤-gal/␤-gal mice perform significantly better (P < 0.01) on a rotating rod than do wt littermates. We have also noted a lower body weight gain (P < 0.05) in Foxs1 ␤-gal/l␤-gal males on a high-fat diet, and we speculate that dorsomedial hypothalamic neurons, expressing Foxs1, could play a role in regulating body weight via regulation of sympathetic outflow. In support of this, we observed increased levels of uncoupling protein 1 mRNA in Foxs1 ␤-gal/␤-gal mice. This points toward a role for Foxs1 in the integration and processing of neuronal signals of importance for energy turnover and motor function.

Clarification of mural cell coverage of vascular endothelial cells by live imaging of zebrafish

“…To date, contribution of neural crest cells to brain MCs has been demonstrated in vertebrates including mice, bird and zebrafish (Etchevers et al, 2001;Heglind et al, 2005;Korn et al, 2002;Trost et al, 2013;Wang et al, 2014;Yamanishi et al, 2012). In agreement with this, our analyses indicated a neural crest origin of MCs in the anterior part of the brain and in the hyaloid vessels.…”

Developmental expression of δ‐opioid receptors during maturation of the parasympathetic, sympathetic, and sensory innervations of the neonatal heart: Early targets for opioid regulation of autonomic control

“…It specifically stains primary afferent neurons in rats, as shown by previous publications (Heglind et al, 2005, Yasuhara et al, 2008Krajnik et al, 2009Krajnik et al, , 2010Mousa et al, 2010). SP-specific immunolabeling with this antibody in rat brain was completely abolished by preabsorption with the synthetic SP peptide (Yasuhara et al, 2008).…”

Foxf2 Is Required for Brain Pericyte Differentiation and Development and Maintenance of the Blood-Brain Barrier

“…Foxf2 expression is also seen in the perineural mesenchyme around the mid-and forebrain ( Figure 1C) and is from E11.5 associated with blood vessels throughout the brain ( Figures 1D-1F). This pattern is characteristic of neural crest-derived progenitors of CNS mural cells, which migrate anteriorly/ventrally in the perineural mesenchyme and enter the neuroectoderm along the paths of the angiogenic sprouts that penetrate the developing brain from the surrounding vascular plexus (Daneman et al, 2010;Heglind et al, 2005;Yamanishi et al, 2012). No Foxf2 expression was seen associated with blood vessels outside the brain ( Figures 1B and 1E).…”

“…Foxf2+ nuclei were associated with blood vessels (identified by isolectin staining) inside the brain ( Figures 1G and 1I) but not in head mesenchyme ( Figure 1K) and were absent from Foxf2 À/À embryos ( Figures 1H, 1J, and 1L). In embryos with a lacZ knockin allele of Foxs1, a neural crest marker that in mid-and forebrain is expressed only in vascular mural cells (Heglind et al, 2005), Foxf2 co-localized with the b-gal+ nuclei of Foxs1 lacZ -expressing cells, both in the perineural mesenchyme ( Figures 1M and 1O) and in the brain ( Figure 1M, inset). The specificity was verified by the absence of nuclear staining in sections from Foxf2 À/À embryos ( Figures 1N and 1P).…”

“…The origin of mammalian mural cells has not been as rigorously traced, but marker analysis suggests that neural crest contributes most, if not all, perivascular cells also in the posterior parts of the brain (Armulik et al, 2011;Heglind et al, 2005). To what extent induction of BBB relies on unique properties of CNS pericytes is not well understood, but lineage does not appear to be critical, because mural cells of thymus and some craniofacial tissues are derived from neural crest (Etchevers et al, 2001;Foster et al, 2008), and avian CNS pericytes are of mixed origin.…”