Change search
ReferencesLink to record
Permanent link

Direct link
The Drosophila LEM-domain protein MAN1 antagonizes BMP signaling at the neuromuscular junction and the wing crossveins
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Developmental Biology.
Show others and affiliations
2010 (English)In: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 339, no 1, 1-13 p.Article in journal (Refereed) Published
Abstract [en]

BMP signaling responses are refined by distinct secreted and intracellular antagonists in different cellular and temporal contexts. Here, we show that the nuclear LEM-domain protein MAN1 is a tissue-specific antagonist of BMP signaling in Drosophila. MAN1 contains two potential Mad-binding sites. We generated MAN1DeltaC mutants, harbouring a MAN1 protein that lacks part of the C-terminus including the RNA recognition motif, a putative Mad-binding domain. MAN1DeltaC mutants show wing crossvein (CV) patterning defects but no detectable alterations in nuclear morphology. MAN1(DeltaC) pupal wings display expanded phospho-Mad (pMad) accumulation and ectopic expression of the BMP-responsive gene crossveinless-2 (cv-2) indicating that MAN1 restricts BMP signaling. Conversely, MAN1 overexpression in wing imaginal discs inhibited crossvein development and BMP signaling responses. MAN1 is expressed at high levels in pupal wing veins and can be activated in intervein regions by ectopic BMP signaling. The specific upregulation of MAN1 in pupal wing veins may thus represent a negative feedback circuit that limits BMP signaling during CV formation. MAN1DeltaC flies also show reduced locomotor activity, and electrophysiology recordings in MAN1DeltaC larvae uncover a new presynaptic role of MAN1 at the neuromuscular junction (NMJ). Genetic interaction experiments suggest that MAN1 is a BMP signaling antagonist both at the NMJ and during CV formation.

Place, publisher, year, edition, pages
2010. Vol. 339, no 1, 1-13 p.
Keyword [en]
MAN1; LEM-domain protein; Inner nuclear membrane; BMP signaling; Mad; Drosophila; Neuromuscular junction; Crossvein; Pupal wing
National Category
Natural Sciences
URN: urn:nbn:se:su:diva-44870DOI: 10.1016/j.ydbio.2009.11.036ISI: 000274870700001PubMedID: 20036230OAI: diva2:362801
authorCount :7Available from: 2010-11-09 Created: 2010-11-09 Last updated: 2010-12-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Samakovlis, Christos
By organisation
Developmental Biology
In the same journal
Developmental Biology
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 370 hits
ReferencesLink to record
Permanent link

Direct link