Border formation in a Bmp gradient reduced to single dissociated cells

Conversions of signaling gradients into sharp "all-or-none" borders are fundamental to tissue and organismal development. However, whether such conversions can be meaningfully reduced to dissociated cells in culture has been uncertain. Here we describe ultrasensitivity, the phenomenon equi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-03, Vol.105 (9), p.3398-3403
Main Authors: Hu, Jia Sheng, Doan, Linda T, Currle, D. Spencer, Paff, Michelle, Rheem, Justin Y, Schreyer, Rachel, Robert, Benoit, Monuki, Edwin S
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins - pharmacology
Brain
Cell culture
Cell culture techniques
Cell lines
Cells
Cultured cells
Embryo, Mammalian
Embryonic stem cells
Forebrain
Gene expression
Gene Expression Regulation
Humans
In Vitro Techniques
Inductive reasoning
Mice
MSX1 Transcription Factor - genetics
Mutation
Neural stem cells
Neurons
Neurons - cytology
Prosencephalon - cytology
Proteins
RNA, Messenger
Signal transduction
Stem cells
Stem Cells - cytology
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Summary:Conversions of signaling gradients into sharp "all-or-none" borders are fundamental to tissue and organismal development. However, whether such conversions can be meaningfully reduced to dissociated cells in culture has been uncertain. Here we describe ultrasensitivity, the phenomenon equivalent to an all-or-none response, in dissociated neural precursor cells (NPCs) exposed to bone morphogenetic protein 4 (Bmp4). NPC ultrasensitivity is evident at the population and single-cell levels based on Msx1 induction, a well known Bmp target response, and occurs in the context of gene expression changes consistent with Bmp4 activity as a morphogen. Dissociated NPCs also display immediate early kinetics and irreversibility for Msx1 induction after brief Bmp4 exposure, which are attractive features for initial border formation. Relevance to border formation in vivo is provided by Bmp4 gain-of-function studies in explants and evidence for single-cell ultrasensitivity in normal and mutant Bmp gradient contexts in the developing forebrain. Together, these studies demonstrate relatively simple, robust, and reducible cell-intrinsic properties that contribute to developmental border formation within a signaling gradient.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0709100105