The SMN binding protein Gemin2 is not involved in motor axon outgrowth

Dev Neurobiol. 2008 Feb 1;68(2):182-94. doi: 10.1002/dneu.20582.

Abstract

A paramount question in spinal muscular atrophy (SMA) research is why reduced levels of SMN, a ubiquitously expressed protein, leads to a motoneuron-specific disease. It has been hypothesized that SMN may have a dual function: a role in snRNP assembly and a novel function that affects axons. We have previously shown that decreasing Smn levels in zebrafish causes defects in motor axon outgrowth. To determine whether decreasing other components of the snRNP complex would also cause motor axon defects, we knocked down Gemin2, a SMN binding protein involved in snRNP assembly. Moderate knockdown of Gemin2 yields a large percentage of morphologically abnormal embryos with shortened trunks and overall delayed development. Examination of motor axons revealed that only embryos with abnormal body morphology had aberrant motor axons indicating that the motor axon defects are secondary to the overall body defects observed in these embryos. To directly test this, we knocked down Gemin2 specifically in motoneurons using two separate approaches and found that motor axons developed normally. Furthermore, wild-type neurons transplanted into morphologically abnormal gemin2 morphants had aberrant motor axons indicating that the motor axon defects observed when Gemin2 is decreased are secondary to the defects in body morphology. These data show that reduction of Gemin2, unlike reduction of SMN, in zebrafish embryos does not directly cause motor axon outgrowth defects. Since Gemin2 and SMN both function in snRNP biogenesis yet only SMN knockdown causes motor axon defects, these data are consistent with an additional role for SMN that is snRNP independent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Down-Regulation / genetics
  • Embryonic Development / physiology
  • Gene Expression Regulation, Developmental / genetics
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Intracellular Signaling Peptides and Proteins
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / innervation
  • Nerve Tissue Proteins / metabolism*
  • RNA Interference
  • RNA-Binding Proteins / metabolism*
  • Ribonucleoproteins, Small Nuclear / genetics
  • Ribonucleoproteins, Small Nuclear / metabolism
  • SMN Complex Proteins
  • Survival of Motor Neuron 1 Protein
  • Zebrafish / embryology*
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Carrier Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • SMN Complex Proteins
  • Sip1 protein, mouse
  • Survival of Motor Neuron 1 Protein
  • Zebrafish Proteins
  • gemin2 protein, zebrafish
  • smn1 protein, zebrafish