Home LiteratureArticle Details
PMID: 15743826 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inactivation of the Sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system.

Molecular and cellular biology ·Vol. 25 ·No. 6 ·2005-03-00 ·Pages 2310-9

Fiore R, Rahim B, Christoffels VM, Moorman AF, Püschel AW

Abstract

The semaphorins are a large family of proteins involved in the patterning of both the vascular and the nervous systems. In order to analyze the function of the membrane-bound semaphorin 5A (Sema5A), we generated mice homozygous for a null mutation in the Sema5a gene. Homozygous null mutants die between embryonic development days 11.5 (E11.5) and E12.5, indicating an essential role of Sema5A during embryonic development. Mutant embryos did not show any morphological defects that could account for the lethality of the mutation. A detailed analysis of the vascular system uncovered a role of Sema5A in the remodeling of the cranial blood vessels. In Sema5A null mutants, the complexity of the hierarchically organized branches of the cranial cardinal veins was decreased. Our results represent the first genetic analysis of the function of a class 5 semaphorin during embryonic development and identify a role of Sema5A in the regional patterning of the vasculature.

MeSH Terms
Animals Body Patterning Cerebral Veins/abnormalities,embryology Embryo, Mammalian/abnormalities,cytology Gene Silencing Genes, Lethal/genetics Homozygote Membrane Proteins/genetics,physiology Mice Mice, Knockout Mutation/genetics Nerve Tissue Proteins/genetics,physiology Semaphorins Skull/blood supply Stem Cells/physiology Veins/embryology
Chemicals
Membrane Proteins Nerve Tissue Proteins Sema5A protein, mouse Semaphorins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Fiore Roberto
Abteilung Molekularbiologie, Institut für Allgemeine Zoologie und Genetik, Westfälische Wilhelms-Universität Münster, Schlossplatz 5, D-48149 Münster, Germany.
Rahim Belquis
Christoffels Vincent M
Moorman Antoon F M
Püschel Andreas W
References (51)
51 references, click to expand
  1. An oligodendrocyte lineage-specific semaphorin, Sema5A, inhibits axon growth by retinal ganglion cells.
    J Neurosci. 2004 May 26;24(21):4989-99 PMID: 15163691
  2. Sensitive nonradioactive detection of mRNA in tissue sections: novel application of the whole-mount in situ hybridization protocol.
    J Histochem Cytochem. 2001 Jan;49(1):1-8 PMID: 11118473
  3. PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development.
    Dev Cell. 2004 Jul;7(1):107-16 PMID: 15239958
  4. Semaphorin-plexin signaling guides patterning of the developing vasculature.
    Dev Cell. 2004 Jul;7(1):117-23 PMID: 15239959
  5. Semaphorin 3A stimulates neurite extension and regulates gene expression in PC12 cells.
    J Biol Chem. 2004 Jul 23;279(30):30923-6 PMID: 15155748
  6. Synapsin I (protein I), a nerve terminal-specific phosphoprotein. III. Its association with synaptic vesicles studied in a highly purified synaptic vesicle preparation.
    J Cell Biol. 1983 May;96(5):1374-88 PMID: 6404912
  7. Localized expression of the atrial natriuretic factor gene during cardiac embryogenesis.
    Genes Dev. 1987 Sep;1(7):693-8 PMID: 2962900
  8. Thrombospondin and a 140 kd fragment promote adhesion and neurite outgrowth from embryonic central and peripheral neurons and from PC12 cells.
    Neuron. 1991 Aug;7(2):231-7 PMID: 1873028
  9. Thrombospondin promotes process outgrowth in neurons from the peripheral and central nervous systems.
    Dev Biol. 1992 Apr;150(2):256-65 PMID: 1551474
  10. Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5.
    Genes Dev. 1995 Jul 1;9(13):1654-66 PMID: 7628699
  11. Developmental regulation of connexin 40 gene expression in mouse heart correlates with the differentiation of the conduction system.
    Dev Dyn. 1995 Dec;204(4):358-71 PMID: 8601030
  12. A novel class of murine semaphorins with homology to thrombospondin is differentially expressed during early embryogenesis.
    Mech Dev. 1996 Jun;57(1):33-45 PMID: 8817451
  13. Semaphorin III is needed for normal patterning and growth of nerves, bones and heart.
    Nature. 1996 Oct 10;383(6600):525-8 PMID: 8849723
  14. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development.
    Development. 1996 Oct;122(10):2977-86 PMID: 8898212
  15. Developmental changes of connexin40 and connexin43 mRNA distribution patterns in the rat heart.
    Cardiovasc Res. 1996 Nov;32(5):886-900 PMID: 8944820
  16. Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection.
    Neuron. 1997 Sep;19(3):519-30 PMID: 9331345
  17. Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice.
    Neuron. 1997 Nov;19(5):995-1005 PMID: 9390514
  18. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor.
    Cell. 1998 Mar 20;92(6):735-45 PMID: 9529250
  19. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis.
    Genes Dev. 1999 Feb 1;13(3):295-306 PMID: 9990854
  20. Heart specific expression of mouse BMP-10 a novel member of the TGF-beta superfamily.
    Mech Dev. 1999 Feb;80(2):181-4 PMID: 10072785
  21. A requirement for neuropilin-1 in embryonic vessel formation.
    Development. 1999 Nov;126(21):4895-902 PMID: 10518505
  22. Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins.
    Science. 2005 Jan 14;307(5707):265-8 PMID: 15550623
  23. PPAR gamma is required for placental, cardiac, and adipose tissue development.
    Mol Cell. 1999 Oct;4(4):585-95 PMID: 10549290
  24. Mechanisms involved in valvuloseptal endocardial cushion formation in early cardiogenesis: roles of transforming growth factor (TGF)-beta and bone morphogenetic protein (BMP).
    Anat Rec. 2000 Feb 1;258(2):119-27 PMID: 10645959
  25. Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins.
    Neuron. 2000 Jan;25(1):29-41 PMID: 10707970
  26. Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections.
    Neuron. 2000 Jan;25(1):43-56 PMID: 10707971
  27. Chamber formation and morphogenesis in the developing mammalian heart.
    Dev Biol. 2000 Jul 15;223(2):266-78 PMID: 10882515
  28. Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development.
    Mol Cell. 2000 Jul;6(1):109-16 PMID: 10949032
  29. Vascular-specific growth factors and blood vessel formation.
    Nature. 2000 Sep 14;407(6801):242-8 PMID: 11001067
  30. Semaphorin 3A is required for guidance of olfactory axons in mice.
    J Neurosci. 2000 Oct 15;20(20):7691-7 PMID: 11027230
  31. Characterization and mutant analysis of the Drosophila sema 5c gene.
    Dev Dyn. 2001 Jul;221(3):322-30 PMID: 11458392
  32. Plexin-A3 mediates semaphorin signaling and regulates the development of hippocampal axonal projections.
    Neuron. 2001 Oct 25;32(2):249-63 PMID: 11683995
  33. Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption.
    Development. 2001 Aug;128(16):3061-70 PMID: 11688556
  34. Targeting of both mouse neuropilin-1 and neuropilin-2 genes severely impairs developmental yolk sac and embryonic angiogenesis.
    Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3657-62 PMID: 11891274
  35. Signaling pathways in vascular development.
    Annu Rev Cell Dev Biol. 2002;18:541-73 PMID: 12142271
  36. Pax6 is required for the normal development of the forebrain axonal connections.
    Development. 2002 Nov;129(21):5041-52 PMID: 12397112
  37. Invariant Sema5A inhibition serves an ensheathing function during optic nerve development.
    Development. 2003 Feb;130(4):775-84 PMID: 12506007
  38. The function of semaphorins during nervous system development.
    Front Biosci. 2003 May 1;8:s484-99 PMID: 12700098
  39. Neuropilin-1 conveys semaphorin and VEGF signaling during neural and cardiovascular development.
    Dev Cell. 2003 Jul;5(1):45-57 PMID: 12852851
  40. Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function.
    Nature. 2003 Jul 24;424(6947):391-7 PMID: 12879061
  41. Semaphorin 3F is critical for development of limbic system circuitry and is required in neurons for selective CNS axon guidance events.
    J Neurosci. 2003 Jul 30;23(17):6671-80 PMID: 12890759
  42. Blood vessels and nerves: common signals, pathways and diseases.
    Nat Rev Genet. 2003 Sep;4(9):710-20 PMID: 12951572
  43. Cardiac chamber formation: development, genes, and evolution.
    Physiol Rev. 2003 Oct;83(4):1223-67 PMID: 14506305
  44. Drosophila screening model for metastasis: Semaphorin 5c is required for l(2)gl cancer phenotype.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11463-8 PMID: 14500904
  45. An essential role of Bmp4 in the atrioventricular septation of the mouse heart.
    Genes Dev. 2003 Oct 1;17(19):2362-7 PMID: 12975322
  46. Controlling the angiogenic switch: a balance between two distinct TGF-b receptor signaling pathways.
    Trends Cardiovasc Med. 2003 Oct;13(7):301-7 PMID: 14522471
  47. Endothelial-pericyte interactions in angiogenesis.
    Cell Tissue Res. 2003 Oct;314(1):15-23 PMID: 12883993
  48. Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2.
    Genes Dev. 2004 Feb 15;18(4):435-47 PMID: 14977921
  49. Semaphorin 3A-mediated axon guidance regulates convergence and targeting of P2 odorant receptor axons.
    Eur J Neurosci. 2004 Apr;19(7):1800-10 PMID: 15078553
  50. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis.
    Development. 2004 May;131(9):2219-31 PMID: 15073151
  51. Plexin-B3 is a functional receptor for semaphorin 5A.
    EMBO Rep. 2004 Jul;5(7):710-4 PMID: 15218527
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.6.2310-2319.2005
Published
2005-03-00
Pages
2310-9
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1061610
Subset
IM
Corrections
ErratumIn
PMID: 32989048
External Links
PubMed source DOI: 10.1128/MCB.25.6.2310-2319.2005 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2