Abstract
BackgroundVertebrates show clear asymmetry in left-right (L-R) patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist.ResultsA L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1), as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM). LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node.ConclusionLeft LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make Ablim1 a candidate for controlling aspects of L-R identity and patterning.
Highlights
Vertebrates show clear asymmetry in left-right (L-R) patterning of their organs and associated vasculature
The lateral plate expression broadly mirrors that of Nodal, yet uniquely for a left lateral plate mesoderm (LPM) expressed locus, we demonstrate that it can be asymmetrically expressed in the absence of detectable LPM Nodal
We investigated the temporospatial distribution of the transcripts encoding these isoforms using wholemount in situ hybridisation (WISH) probes hybridising to different portions of the actin binding lim protein 1 (Ablim1) message; probes corresponding to the beginning (Ex 2-6), the common region (Ex 8-25) and the 3'untranslated region (UTR) (3'UTRa and b; Fig. 1)
Summary
Vertebrates show clear asymmetry in left-right (L-R) patterning of their organs and associated vasculature. The. During mammalian development, the first morphological sign of L-R asymmetry is the looping of the primitive heart tube, initially to the right. The first morphological sign of L-R asymmetry is the looping of the primitive heart tube, initially to the right After this the embryo begins to undergo embryonic turning, the pro-. Cess that results in the embryo taking up the classic foetal position This occurs in a L-R asymmetric manner such that the caudal-most region of the embryo passes to the right side of the head. These morphological asymmetries are, prefigured by molecular asymmetries. Work over the past decade has resulted in a broadly accepted model explaining how L-R asymmetry is established in the mammalian embryo (reviewed [4])
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
