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A genetic cascade involving the genes klumfuss, nab and castor specifies the abdominal leucokinergic neurons in the Drosophila CNS
Centro de Biología Molecular-Severo Ochoa, Universidad Autónoma de Madrid-C.S.I.C., Madrid, Spain.
Centro de Biología Molecular-Severo Ochoa, Universidad Autónoma de Madrid-C.S.I.C., Madrid, Spain.
Centro de Biología Molecular-Severo Ochoa, Universidad Autónoma de Madrid-C.S.I.C., Madrid, Spain.
Linköping University, Department of Clinical and Experimental Medicine, Developmental Biology, IKE. Linköping University, Faculty of Health Sciences.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The genetic mechanisms underlying the specification of a large number of different cell fates starting from a limited group of progenitor cells are a major focus of investigations of central nervous system development. In Drosophila the identities of the different neuronal progenitor cells, the neuroblasts, are specified by a combination of spatial and temporal factors. But how each neuroblast gives rise to a specific repertoire of cell types via a precise programme is poorly understood. In this report we analyse the specification of a small set of peptidergic cells, the abdominal leucokinergic neurons. We identify the progenitors of these neurons, the temporal window in which they are specified, and the influence of the Notch signalling pathway on their specification. We also show that the products of the genes klumfuss, nab and castor play important roles in their specification via a genetic cascade.

Keyword [en]
Drosophila, CNS development, neuronal fate specification, Leucokinin, ABLK
National Category
Developmental Biology
Identifiers
URN: urn:nbn:se:liu:diva-51644OAI: oai:DiVA.org:liu-51644DiVA: diva2:276209
Available from: 2009-11-11 Created: 2009-11-11 Last updated: 2016-11-30Bibliographically approved
In thesis
1. Genetic mechanisms behind cell specification in the Drosophila CNS
Open this publication in new window or tab >>Genetic mechanisms behind cell specification in the Drosophila CNS
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The human central nervous system (CNS) contains a daunting number of cells and tremendous cellular diversity. A fundamental challenge of developmental neurobiology is to address the questions of how so many different types of neurons and glia can be generated at the precise time and place, making precisely the right connections. Resolving this issue involves dissecting the elaborate genetic networks that act within neurons and glia, as well as in the neural progenitor cells that generates them, to specify their identities.

My PhD project has involved addressing a number of unresolved issues pertaining to how neural progenitor cells are specified to generate different types of neurons and glial cells in different temporal and spatial domains, and also how these early temporal and spatial cues are integrated to activate late cell fate determinants, which act in post-mitotic neural cells to activate distinct batteries of terminal differentiation genes.

Analyzing the development of a specific Drosophila melanogaster (Drosophila) CNS stem cell – the neuroblast 5-6 (NB5-6) – we have identified several novel mechanisms of cell fate specification in the Drosophila CNS. We find that, within this lineage, the differential specification of a group of sequentially generated neurons – the Ap cluster neurons – is critically dependent upon the simultaneous triggering of two opposing feed-forward loops (FFLs) within the neuroblast. The first FFL involves cell fate determinants and progresses within the post-mitotic neurons to establish a highly specific combinatorial code of regulators, which activates a distinct battery of terminal differentiation genes. The second loop, which progresses in the neuroblast, involves temporal and sub-temporal genes that together oppose the progression of the first FFL. This leads to the establishment of an alternative code of regulators in late-born Ap cluster neurons, whereby alternative cell fates are specified. Furthermore, we find that the generation and specification of the Ap cluster neurons is modulated along the neuraxis by two different mechanisms. In abdominal segments, Hox genes of the Bithorax cluster integrates with Pbx/Meis factors to instruct NB5-6 to leave the cell cycle before the Ap cluster neurons are generated. In brain segments, Ap cluster neuron equivalents are generated, but improperly specified due to the absence of the proper Hox and temporal code. Additionally, in thoracic segments we find that the specification of the Ap cluster neurons is critically dependent upon the integration of the Hox, Pbx/Meis, and the temporal genes, in the activation of the critical cell fate determinant FFL.

We speculate that the developmental principles of (i) feed-forward combinatorial coding; (ii) simultaneously triggered yet opposing feed-forward loops; and (iii) integration of different Hox, Pbx/Meis, and temporal factors, at different axial levels to control inter-segmental differences in lineage progression and specification; might be used widely throughout the animal kingdom to generate cell type diversity in the CNS.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 104 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1157
Keyword
Drosophila melanogaster, nervous system development, cell specification, stem cells, cell proliferation, combinatorial coding, feedforward loop
National Category
Developmental Biology
Identifiers
urn:nbn:se:liu:diva-51637 (URN)978-91-7393-483-1 (ISBN)
Public defence
2009-12-04, Hörsal Linden, Campus US, Linköpings universitet, Linköping, 00:00 (English)
Opponent
Supervisors
Available from: 2009-11-13 Created: 2009-11-11 Last updated: 2016-11-30Bibliographically approved

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Baumgardt, MagnusThor, Stefan

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