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Published on: May 17, 2016
Differential expression of a transcription regulatory factor, the LIM domain only 4 protein Lmo4, in muscle sensory
Hsiao-Huei Chen1, Joseph W Yip, Alexandre F R Stewart
1Department of Neurobiology, University of Pittsburgh, PA 15261, USA.
Abstract:
In the stretch-reflex system, proprioceptive sensory neurons make selective synaptic connections with different subsets of motoneurons, according to the peripheral muscles they supply. To examine the molecular mechanisms that may influence the selection of these synaptic targets, we constructed single-cell cDNA libraries from sensory neurons that innervate antagonist muscles. Differential screening of these libraries identified a transcription regulatory co-factor of the LIM homeodomain proteins, the LIM domain only 4 protein Lmo4, expressed in most adductor but few sartorius sensory neurons. Differential patterns of Lmo4 expression were also seen in sensory neurons supplying three other muscles. A subset of motoneurons also expresses Lmo4 but the pattern of expression is not specific for motor pools. Differential expression of Lmo4 occurs early, as neurons develop their characteristic LIM homeodomain protein expression patterns. Moreover, ablation of limb buds does not block Lmo4 expression, suggesting that an intrinsic program controls the early differential expression of Lmo4. LIM homeodomain proteins are known to regulate several aspects of sensory and motor neuronal development. Our results suggest that Lmo4 may participate in this differentiation by regulating the transcriptional activity of LIM homeodomain proteins.
Insights
The LIM domain only 4 (Lmo4) protein is differentially expressed in sensory neurons, suggesting it plays a role in the development of neuronal connections within the stretch-reflex system.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Proprioceptive sensory neurons form specific synaptic connections with motoneurons.
- Understanding the molecular mechanisms guiding these selective connections is crucial for neuronal development research.
Purpose of the Study:
- To investigate the molecular factors influencing target selection by sensory neurons in the stretch-reflex system.
- To identify genes with differential expression patterns in sensory neurons innervating antagonist muscles.
Main Methods:
- Construction of single-cell cDNA libraries from sensory neurons innervating antagonist muscles.
- Differential screening of cDNA libraries to identify unique gene expression profiles.
- Analysis of Lmo4 expression patterns in developing neurons and motoneurons.
Main Results:
- The LIM domain only 4 (Lmo4) protein, a co-factor for LIM homeodomain proteins, shows differential expression in sensory neurons supplying specific muscles.
- Lmo4 expression is observed early in neuronal development and appears to be controlled by an intrinsic program.
- While some motoneurons express Lmo4, its expression pattern is not specific to motor pools.
Conclusions:
- Lmo4 may be involved in the differentiation of sensory neurons by modulating the transcriptional activity of LIM homeodomain proteins.
- The findings suggest Lmo4 plays a role in the precise wiring of the nervous system during development.
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