TY - JOUR
T1 - Cell-type specific regulation of serotonergic identity by the C. elegans LIM-homeodomain factor LIM-4
AU - Zheng, Xianwu
AU - Chung, Shinjae
AU - Tanabe, Takahiro
AU - Sze, Ji Ying
N1 - Funding Information:
We thank Dr. M. Labouesse for anti-LIN-26 antibody, Dr. O. Hobert for lim-4 ∷ gfp reporters, K. Shi and A. Powell for their contribution during early stages of yz12 cloning, T. Stiernagle and the Caenorhabditis Genetics Center for worm strains, and the C. elegans Knockout Consortium for deletion mutants. This work is supported by grants from Whitehall foundation and the National Institutes of Mental Health (to J. S.).
PY - 2005/10/15
Y1 - 2005/10/15
N2 - How a common neurotransmitter phenotype specified in neurons of different origins is an outstanding issue in neuronal development and function. In C. elegans larvae, serotonin is synthesized in 2 pairs of neurons, the secretory neurons NSM and the chemosensory neurons ADF. In order to delineate the molecular mechanisms of serotonergic phenotype establishment, we have screened for neuron-specific serotonin deficient (nss) mutants. Our prior study showed that the POU-homeodomain factor UNC-86 is expressed in and required for the NSM neurons to adopt serotonergic phenotype and correct pathfinding, whereas ADF are unaffected in unc-86-null mutants. Here, we report that the LIM-homeodomain factor LIM-4 regulates ADF serotonergic phenotype. In lim-4 mutants, many aspects of ADF differentiation occur, however, they fail to express serotonin phenotype and exhibit aberrant cilia properties. LIM-4 expression rises in the neuroblast that produces two distinct neurons: ADF and the olfactory neuron AWB. We show that lim-4 is regulated by separable mechanisms to determine disparate subtype identities in these two neuronal types. In vivo promoter analyses reveal that cis-element(s) within introns are necessary and sufficient to direct lim-4 to specify serotonergic phenotype, whereas its 5′-upstream sequence directs lim-4 function in AWB. Thus, a transcription factor may act independently to specify distinct differentiation traits in two sister cells. We propose that serotonergic identity is specified in cell-specific contexts to coordinate the development and function.
AB - How a common neurotransmitter phenotype specified in neurons of different origins is an outstanding issue in neuronal development and function. In C. elegans larvae, serotonin is synthesized in 2 pairs of neurons, the secretory neurons NSM and the chemosensory neurons ADF. In order to delineate the molecular mechanisms of serotonergic phenotype establishment, we have screened for neuron-specific serotonin deficient (nss) mutants. Our prior study showed that the POU-homeodomain factor UNC-86 is expressed in and required for the NSM neurons to adopt serotonergic phenotype and correct pathfinding, whereas ADF are unaffected in unc-86-null mutants. Here, we report that the LIM-homeodomain factor LIM-4 regulates ADF serotonergic phenotype. In lim-4 mutants, many aspects of ADF differentiation occur, however, they fail to express serotonin phenotype and exhibit aberrant cilia properties. LIM-4 expression rises in the neuroblast that produces two distinct neurons: ADF and the olfactory neuron AWB. We show that lim-4 is regulated by separable mechanisms to determine disparate subtype identities in these two neuronal types. In vivo promoter analyses reveal that cis-element(s) within introns are necessary and sufficient to direct lim-4 to specify serotonergic phenotype, whereas its 5′-upstream sequence directs lim-4 function in AWB. Thus, a transcription factor may act independently to specify distinct differentiation traits in two sister cells. We propose that serotonergic identity is specified in cell-specific contexts to coordinate the development and function.
KW - C. elegans
KW - LIM-homeodomain factors
KW - Neuron-specific enhancers
KW - Sensory property
KW - Serotonin identity
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U2 - 10.1016/j.ydbio.2005.08.013
DO - 10.1016/j.ydbio.2005.08.013
M3 - Article
C2 - 16168406
AN - SCOPUS:26644455278
SN - 0012-1606
VL - 286
SP - 618
EP - 628
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -