Sushi repeat-containing protein X-linked 2: A novel phylogenetically conserved hypothalamo-pituitary protein

Research output: Contribution to journalArticleScientificpeer-review


  • Mehwish Anwer
  • Tamuna Bolkvadze
  • Xavier Ekolle Ndode-Ekane
  • Noora Puhakka
  • Tuomas Rauramaa
  • Ville Leinonen
  • Erwin A. van Vliet
  • Dick F. Swaab
  • Annakaisa Haapasalo
  • Stina Leskela
  • Nea Bister
  • Tarja Malm
  • Synnove Carlson
  • Eleonora Aronica
  • Asla Pitkanen

Research units

  • University of Eastern Finland
  • Kuopio University Hospital
  • University of Amsterdam
  • Netherlands Institute for Neuroscience


Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel protein associated with language development, synaptic plasticity, tissue remodeling, and angiogenesis. We investigated the expression and spatial localization of SRPX2 in normal mouse, rat, monkey, and human brain using in situ hybridization and immunohistochemistry. Antibody specificity was determined using in vitro siRNA based silencing of SRPX2. Cell type-specific expression was verified by double-labeling with oxytocin or vasopressin. Western blot was used to detect SRPX2 protein in rat and human plasma and cerebrospinal fluid. Unexpectedly, SRPX2 mRNA expression levels were strikingly higher in the hypothalamus as compared to the cortex. All SRPX2 immunoreactive (ir) neurons were localized in the hypothalamic paraventricular, periventricular, and supraoptic nuclei in mouse, rat, monkey, and human brain. SRPX2 colocalized with vasopressin or oxytocin in paraventricular and supraoptic neurons. Hypothalamic SRPX2-ir positive neurons gave origin to dense projections traveling ventrally and caudally toward the hypophysis. Intense axonal varicosities and terminal arborizations were identified in the rat and human neurohypophysis. SRPX2-ir cells were also found in the adenohypophysis. Light SRPX2-ir projections were observed in the dorsal and ventral raphe, locus coeruleus, and the nucleus of the solitary tract in mouse, rat and monkey. SRPX2 protein was also detected in plasma and CSF. Our data revealed intense phylogenetically conserved expression of SRPX2 protein in distinct hypothalamic nuclei and the hypophysis, suggesting its active role in the hypothalamo-pituitary axis. The presence of SRPX2 protein in the plasma and CSF suggests that some of its functions depend on secretion into body fluids.


Original languageEnglish
Pages (from-to)1806-1819
Number of pages14
Issue number11
Publication statusPublished - 1 Aug 2018
MoE publication typeA1 Journal article-refereed

    Research areas

  • hypophysis, hypothalamus, oxytocin, paraventricular nucleus, supraoptic nucleus, Sushi repeat-containing protein X-Linked 2, vasopressin, RRID:AB_2050340, RRID:AB_2157626, RRID:AB_2721268, RRID:AB_90782, RRID:AB_2314534, RRID:AB_321301, TRAUMATIC BRAIN-INJURY, PARAVENTRICULAR NUCLEUS, COLORECTAL-CANCER, GASTRIC-CANCER, SRPX2, SPEECH, DYSFUNCTION, DISORDERS, MIGRATION, OXYTOCIN

ID: 27449073