Specification of neuronal identities by feedforward combinatorial coding.

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Title: Specification of neuronal identities by feedforward combinatorial coding.
Authors: Baumgardt, M
Miguel-Aliaga, I
Karlsson, D
Ekman, H
Thor, S
Item Type: Journal Article
Abstract: Neuronal specification is often seen as a multistep process: earlier regulators confer broad neuronal identity and are followed by combinatorial codes specifying neuronal properties unique to specific subtypes. However, it is still unclear whether early regulators are re-deployed in subtype-specific combinatorial codes, and whether early patterning events act to restrict the developmental potential of postmitotic cells. Here, we use the differential peptidergic fate of two lineage-related peptidergic neurons in the Drosophila ventral nerve cord to show how, in a feedforward mechanism, earlier determinants become critical players in later combinatorial codes. Amongst the progeny of neuroblast 5-6 are two peptidergic neurons: one expresses FMRFamide and the other one expresses Nplp1 and the dopamine receptor DopR. We show the HLH gene collier functions at three different levels to progressively restrict neuronal identity in the 5-6 lineage. At the final step, collier is the critical combinatorial factor that differentiates two partially overlapping combinatorial codes that define FMRFamide versus Nplp1/DopR identity. Misexpression experiments reveal that both codes can activate neuropeptide gene expression in vast numbers of neurons. Despite their partially overlapping composition, we find that the codes are remarkably specific, with each code activating only the proper neuropeptide gene. These results indicate that a limited number of regulators may constitute a potent combinatorial code that dictates unique neuronal cell fate, and that such codes show a surprising disregard for many global instructive cues.
Issue Date: 6-Feb-2007
Date of Acceptance: 6-Dec-2006
URI: http://hdl.handle.net/10044/1/30017
DOI: https://dx.doi.org/10.1371/journal.pbio.0050037
ISSN: 1545-7885
Publisher: Public Library of Science
Journal / Book Title: PLOS Biology
Volume: 5
Issue: 2
Copyright Statement: © 2007 Baumgardt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Animals
Cell Differentiation
Cell Lineage
Drosophila
Drosophila Proteins
Eye Proteins
FMRFamide
Gene Expression Regulation, Developmental
Homeodomain Proteins
LIM-Homeodomain Proteins
Membrane Proteins
Neurons
Neuropeptides
Receptors, Dopamine
Signal Transduction
Transcription Factors
Neurons
Animals
Drosophila
Neuropeptides
FMRFamide
Homeodomain Proteins
Eye Proteins
Drosophila Proteins
Membrane Proteins
Receptors, Dopamine
Transcription Factors
Signal Transduction
Cell Differentiation
Gene Expression Regulation, Developmental
Cell Lineage
LIM-Homeodomain Proteins
Animals
Cell Differentiation
Cell Lineage
Drosophila
Drosophila Proteins
Eye Proteins
FMRFamide
Gene Expression Regulation, Developmental
Homeodomain Proteins
LIM-Homeodomain Proteins
Membrane Proteins
Neurons
Neuropeptides
Receptors, Dopamine
Signal Transduction
Transcription Factors
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Publication Status: Published
Article Number: e37
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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