Single-stranded DNA binding proteins are required for LIM complexes to induce transcriptionally active chromatin and specify spinal neuronal identities

Development. 2016 May 15;143(10):1721-31. doi: 10.1242/dev.131284. Epub 2016 Mar 10.

Abstract

LIM homeodomain factors regulate the development of many cell types. However, transcriptional coactivators that mediate their developmental function remain poorly defined. To address these, we examined how two related NLI-dependent LIM complexes, which govern the development of spinal motor neurons and V2a interneurons, activate the transcription in the embryonic spinal cord. We found that single-stranded DNA-binding proteins are recruited to these LIM complexes via NLI, and enhance their transcriptional activation potential. Ssdp1 and Ssdp2 (Ssdp1/2) are highly expressed in the neural tube and promote motor neuron differentiation in the embryonic spinal cord and P19 stem cells. Inhibition of Ssdp1/2 activity in mouse and chick embryos suppresses the generation of motor neurons and V2a interneurons. Furthermore, Ssdp1/2 recruit histone-modifying enzymes to the motor neuron-specifying LIM complex and trigger acetylation and lysine 4 trimethylation of histone H3, which are well-established chromatin marks for active transcription. Our results suggest that Ssdp1/2 function as crucial transcriptional coactivators for LIM complexes to specify spinal neuronal identities during development.

Keywords: Isl1; Ldb1; Lhx3; Motor neuron; NLI; Spinal cord; V2a-interneuron.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning
  • Chick Embryo
  • Chromatin / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryo, Mammalian / metabolism
  • Humans
  • Interneurons / metabolism
  • LIM-Homeodomain Proteins / metabolism*
  • Mice
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Mutation / genetics
  • Neurons / cytology
  • Neurons / metabolism*
  • Protein Binding / genetics
  • Rats
  • Spinal Cord / cytology*
  • Spinal Cord / embryology
  • Spinal Cord / metabolism
  • Trans-Activators / metabolism
  • Transcriptional Activation / genetics*

Substances

  • Chromatin
  • DNA-Binding Proteins
  • LIM-Homeodomain Proteins
  • Trans-Activators