Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors

Soo Kyung Lee; Samuel L. Pfaff

doi:10.1016/S0896-6273(03)00296-4

Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors

Soo Kyung Lee, Samuel L. Pfaff

Research output: Contribution to journal › Article › peer-review

248 Scopus citations

Abstract

Inductive signaling leads to the coactivation of regulatory pathways for specifying general neuronal traits in parallel with instructions for neuronal subtype specification. Nevertheless, the mechanisms that ensure that these pathways are synchronized have not been defined. To address this, we examined how bHLH proteins Ngn2 and NeuroM controlling neurogenesis functionally converge with LIM-homeodomain (LIM-HD) factors Isl1 and Lhx3 involved in motor neuron subtype specification. We found that Ngn2 and NeuroM transcriptionally synergize with Isl1 and Lhx3 to specify motor neurons in the embryonic spinal cord and in P19 stem cells. The mechanism underlying this cooperativity is based on interactions that directly couple the activity of the bHLH and LIM-HD proteins, mediated by the adaptor protein NLI. This functional link acts to synchronize neuronal subtype specification with neurogenesis.

Original language	English (US)
Pages (from-to)	731-745
Number of pages	15
Journal	Neuron
Volume	38
Issue number	5
DOIs	https://doi.org/10.1016/S0896-6273(03)00296-4
State	Published - Jun 5 2003
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0896-6273(03)00296-4

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title = "Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors",

abstract = "Inductive signaling leads to the coactivation of regulatory pathways for specifying general neuronal traits in parallel with instructions for neuronal subtype specification. Nevertheless, the mechanisms that ensure that these pathways are synchronized have not been defined. To address this, we examined how bHLH proteins Ngn2 and NeuroM controlling neurogenesis functionally converge with LIM-homeodomain (LIM-HD) factors Isl1 and Lhx3 involved in motor neuron subtype specification. We found that Ngn2 and NeuroM transcriptionally synergize with Isl1 and Lhx3 to specify motor neurons in the embryonic spinal cord and in P19 stem cells. The mechanism underlying this cooperativity is based on interactions that directly couple the activity of the bHLH and LIM-HD proteins, mediated by the adaptor protein NLI. This functional link acts to synchronize neuronal subtype specification with neurogenesis.",

author = "Lee, {Soo Kyung} and Pfaff, {Samuel L.}",

note = "Funding Information: We are grateful to E. Ruiz for her extensive technical assistance; H. Juguilon and R. Evans for countless Luciferase assays; C. Kintner, G. Gill, T. Jessell, and members of the Pfaff laboratory for numerous suggestions and comments on the manuscript. We thank B. Seed, M. Ballivet, and D. Anderson for providing DNA clones of a synthetic TATA element, NeuroM and Cash1, and Ngn2, respectively. S.-K.L. was supported by a Human Frontiers Science Program postdoctoral fellowship. S.L.P is supported by the PEW, Chun, and Mathers Foundations. This project was funded by the National Institute of Neurological Disorders and Stroke (NINDS).",

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N2 - Inductive signaling leads to the coactivation of regulatory pathways for specifying general neuronal traits in parallel with instructions for neuronal subtype specification. Nevertheless, the mechanisms that ensure that these pathways are synchronized have not been defined. To address this, we examined how bHLH proteins Ngn2 and NeuroM controlling neurogenesis functionally converge with LIM-homeodomain (LIM-HD) factors Isl1 and Lhx3 involved in motor neuron subtype specification. We found that Ngn2 and NeuroM transcriptionally synergize with Isl1 and Lhx3 to specify motor neurons in the embryonic spinal cord and in P19 stem cells. The mechanism underlying this cooperativity is based on interactions that directly couple the activity of the bHLH and LIM-HD proteins, mediated by the adaptor protein NLI. This functional link acts to synchronize neuronal subtype specification with neurogenesis.

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Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors

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