Are there conserved roles for the extracellular matrix, cilia, and junctional complexes in left‐right patterning?

Abstract

Summary: Many different types of molecules have essential roles in patterning the left-right axis and directing asymmetric morphogenesis. In particular, the relationship between signaling molecules and transcription factors has been explored extensively. Another group of proteins implicated in left-right patterning are components of the extracellular matrix, apical junctions, and cilia. These structural molecules have the potential to participate in the conversion of morphogenetic cues from the extracellular environment into morphogenetic patterning via their interactions with the actin cytoskeleton. Although it has been relatively easy to temporally position these proteins within the hierarchy of the left-right patterning pathway, it has been more difficult to define how they mechanistically fit into these pathways. Consequently, our understanding of how these factors impart patterning information to influence the establishment of the left-right axis remains limited. In this review, we will discuss those structural molecules that have been implicated in early phases of left-right axis development. genesis 52:488-502,

Idiopathic Scoliosis Families Highlight Actin-Based and Microtubule-Based Cellular Projections and Extracellular Matrix in Disease Etiology

“…To summarize, we identified three interconnected categories of GO terms that are enriched in our dataset of five IS families: actin-based cellular projections, microtubule-based cellular projections, and the ECM. The ECM is important for both stereocilia (actin-based cellular projections) and cilia (microtubule-based cellular projections), tying together the three functional categories identified in our dataset ( Seeger-Nukpezah and Golemis 2012 ; Collins and Ryan 2014 ; Deans 2013 ). Previous studies support the involvement of each of these individual categories of genes and GO terms in IS etiology.…”

Cilium structure, assembly, and disassembly regulated by the cytoskeleton

“…Primary cilia and cell–cell junctions, including the adherens and tight junctions, have several unifying features — they are markers of cell polarity in epithelia, sites of mechanosensation, transducers of signals, and directly interface with, and are regulated by the actin cytoskeleton. Currently, the relationship between these structures seems to be correlative and indirect [ 169 ]. Fluid shear stress in the renal proximal tubule epithelium causes a loss of polarity markers, including cilia and proteins of adherens and tight junctions [ 170 ].…”

MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates

“…Specific ECM molecules play various roles at the node during left-right patterning 10 , suggesting candidate MMP21 cleavage targets. Also, relevant to the central role of TGFβ family members (e.g.…”