Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed widely in the adult mouse and during embryogenesis

Abstract

Neogenin is a member of the N-CAM family of cell adhesion molecules and is closely related to the DCC tumor suppressor gene product. Recently, it has been demonstrated that the DCC/Neogenin subfamily plays a key role in axonal guidance within the embryonic nervous system, however little is known about the function of DCC or Neogenin in non-neuronal tissues in vertebrates. To gain an understanding of Neogenin function outside of the nervous system we have cloned and sequenced the mouse homologue of Neogenin. We describe three alternatively spliced exons within the extracellular domain of Neogenin and a fourth alternatively spliced exon within the cytoplasmic domain. We further demonstrate that three of these alternatively spliced exons are developmentally regulated. Analysis of Neogenin mRNA expression showed that two distinct Neogenin transcripts are expressed at signi®cant levels in a broad spectrum of adult mouse tissues and throughout the mid to late stages of embryogenesis. In situ hybridization studies on day 15.5 mouse embryos revealed that Neogenin is expressed widely throughout the developing mouse embryo, in both neuronal and nonneuronal tissues. These observations suggests that Neogenin may play an integral role in regulating di erentiation programmes and/or cell migration events within many embryonic and adult tissues.

Evidence That Inhibition of Hemojuvelin Shedding in Response to Iron Is Mediated through Neogenin

“…Neogenin is a membrane protein widely expressed in different tissues including skeletal muscle and liver (22)(23)(24). It is the classical receptor for netrins as well as repulsive guidance molecule a (RGMa), a close family member of HJV (3)(4)(5).…”

“…In addition to BMPs, our previous studies showed that HJV also interacts with neogenin (7). Neogenin is a transmembrane protein widely expressed in different tissues including skeletal muscle and liver (22)(23)(24). It is the classical receptor for netrins as well as RGMa (25,26).…”

Neogenin Regulates Skeletal Myofiber Size and Focal Adhesion Kinase and Extracellular Signal-regulated Kinase Activities In Vivo and In Vitro

“…Furthermore, vascular smooth muscle cells are attracted by and adhere to netrin-1 in a neogenin-dependent manner . Neogenin morphant zebrafish display an aberrant neural tube and defects in somitogenesis, suggesting possible roles in convergent extension and/or cell polarity during formation of the rostrocaudal axis (Mawdsley et al, 2004).Neogenin is expressed throughout the developing mouse embryo but is at high levels in developing skeletal muscle; netrin-1, netrin-3, and RGMc are also expressed in premuscle masses of the mouse embryo Keeling et al, 1997;Wang et al, 1999;Kuninger et al, 2004;Niederkofler et al, 2004;Fitzgerald et al, 2006;Rodriguez et al, 2007). We recently showed that mouse myoblast cell lines and cultured primary myoblasts derived from satellite cells express netrin-3 and neogenin and that these factors promote formation of multinucleated myotubes .…”

c-Jun N-terminal Kinase 1 (JNK1) Is Required for Coordination of Netrin Signaling in Axon Guidance

“…Netrins are a conserved family of canonical guidance cues, functioning as either chemoattractants or chemorepellents in a variety of different species (6 -14). Several vertebrate receptors of Netrins have been identified such as deleted in colorectal cancer (DCC) 4 (13,15), Neogenin (15,16), Uncoordinated-5 (UNC5) (17,18), and Down syndrome cell adhesion molecule (DSCAM) (19,20). Although DCC/UNC40 can mediate attraction and UNC5 mediate repulsion by itself (1,13,15,18,(21)(22)(23)(24), assembling of appropriate receptor complexes is essential for the growth cone steering decision in Netrin signaling.…”