NDLI: Fusion protein Isl1–Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs

Content Provider	PubMed Central
Author	Lee, Seunghee Cuvillier, James M. Lee, Bora Shen, Rongkun Lee, Jae W. Lee, Soo-kyung
Abstract	Combinatorial transcription codes generate the myriad of cell types during development and thus likely provide crucial insights into directed differentiation of stem cells to a specific cell type. The LIM complex composed of Isl1 and Lhx3 directs the specification of spinal motor neurons (MNs) in embryos. Here, we report that Isl1–Lhx3, a LIM-complex mimicking fusion, induces a signature of MN transcriptome and concomitantly suppresses interneuron differentiation programs, thereby serving as a potent and specific inducer of MNs in stem cells. We show that an equimolar ratio of Isl1 and Lhx3 and the LIM domain of Lhx3 are crucial for generating MNs without up-regulating interneuron genes. These led us to design Isl1–Lhx3, which maintains the desirable 1:1 ratio of Isl1 and Lhx3 and the LIM domain of Lhx3. Isl1–Lhx3 drives MN differentiation with high specificity and efficiency in the spinal cord and embryonic stem cells, bypassing the need for sonic hedgehog (Shh). RNA-seq analysis revealed that Isl1–Lhx3 induces the expression of a battery of MN genes that control various functional aspects of MNs, while suppressing key interneuron genes. Our studies uncover a highly efficient method for directed MN generation and MN gene networks. Our results also demonstrate a general strategy of using embryonic transcription complexes for producing specific cell types from stem cells.
Related Links	http://dx.doi.org/10.1073/pnas.1114515109
Ending Page	3388
Page Count	6
Starting Page	3383
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	109
Language	English
Publisher	National Academy of Sciences
Publisher Date	2012-02-28
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Fusion protein Isl1-Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs.

Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity

miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3

Corrigendum: miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3

Critical Roles of the LIM Domains of Lhx3 in Recruiting Coactivators to the Motor Neuron-Specifying Isl1-Lhx3 Complex

Suppression of interneuron programs and maintenance of selected spinal motor neuron fates by the transcription factor AML1/Runx1

miR-218 is Essential to Establish Motor Neuron Fate as a Downstream Effector of Isl1-Lhx3

Corrigendum: miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3

Recombination signal sequence-binding protein Jκ alters mesodermal cell fate decisions by suppressing cardiomyogenesis

Fusion protein Isl1–Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs

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Fusion protein Isl1-Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs.

Islet-to-LMO stoichiometries control the function of transcription complexes that specify motor neuron and V2a interneuron identity

miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3

Corrigendum: miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3

Critical Roles of the LIM Domains of Lhx3 in Recruiting Coactivators to the Motor Neuron-Specifying Isl1-Lhx3 Complex

Suppression of interneuron programs and maintenance of selected spinal motor neuron fates by the transcription factor AML1/Runx1

miR-218 is Essential to Establish Motor Neuron Fate as a Downstream Effector of Isl1-Lhx3

Corrigendum: miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3

Recombination signal sequence-binding protein Jκ alters mesodermal cell fate decisions by suppressing cardiomyogenesis

Fusion protein Isl1–Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs