SSDP cofactors regulate neural patterning and differentiation of specific axonal projections.
The developmental activity of LIM homeodomain transcription factors (LIM-HDs) is critically controlled by LIM domain-interacting cofactors of LIM-HDs (CLIM, also known as NLI or LDB). CLIM cofactors associate with single-stranded DNA binding proteins (SSDPs, also known as SSBPs) thereby recruiting SSDP1 and/or SSDP2 to LIM-HD/CLIM complexes. Although evidence has been presented that SSDPs are important for the activity of specific LIM-HD/CLIM complexes, the developmental roles of SSDPs are unclear. We show that SSDP1a and SSDP1b mRNAs are widely expressed early during zebrafish development with conspicuous expression of SSDP1b in sensory trigeminal and Rohon-Beard neurons. SSDP1 and CLIM immunoreactivity co-localize in these neuronal cell types and in other structures. Over-expression of the N-terminal portion of SSDP1 (N-SSDP1), which contains the CLIM-interaction domain, increases endogenous CLIM protein levels in vivo and impairs the formation of eyes and midbrain-hindbrain boundary. In addition, manipulation of SSDP1 via N-SSDP1 over-expression or SSDP1b knock down impairs trigeminal and Rohon-Beard sensory axon growth. We show that N-SSDP1 is able to partially rescue the inhibition of axon growth induced by a dominant-negative form of CLIM (DN-CLIM). These results reveal specific functions of SSDP in neural patterning and sensory axon growth, in part due to the stabilization of LIM-HD/CLIM complexes.
Centre for Neuroregeneration, School of Biomedical Sciences, University of Edinburgh, The Chancellor's Building, Edinburgh EH16 4SB, UK.
Zhen
Z
Zhong
Hong
H
Ma
Naoko
N
Taniguchi-Ishigaki
Lalitha
L
Nagarajan
Catherina G
CG
Becker
Ingolf
I
Bach
Thomas
T
Becker
D000818:Animals; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D055495:Neurogenesis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D014157:Transcription Factors