A pathway for unicellular tube extension depending on the lymphatic vessel determinant Prox1 and on osmoregulation.

Jan 2013

Kolotuev I, Hyenne V, Schwab Y, Rodriguez D, Labouesse M.

Source

1] IGBMC, Development and Stem Cells Program, CNRS (UMR7104)/INSERM (U964)/Université de Strasbourg, 1 rue Laurent Fries, BP.10142, 67400 Illkirch, France [2].

Abstract

The mechanisms regulating the extension of small unicellular tubes remain poorly defined. Here we identify several steps in Caenorhabditis elegans excretory canal growth, and propose a model for lumen extension. Our results suggest that the basal and apical excretory membranes grow sequentially: the former extends first like an axon growth cone; the latter extends next as a result of an osmoregulatory activity triggering peri-apical vesicles (a membrane reservoir) to fuse with the lumen. An apical cytoskeletal web including intermediate filaments and actin crosslinking proteins ensures straight regular lumengrowth. Expression of several genes encoding proteins mediating excretory lumen extension, such as the osmoregulatory STE20-like kinase GCK-3 and the intermediate filament IFB-1, is regulated by ceh-26 (here referred to as pros-1), which we found essential for excretory canal formation. Interestingly, PROS-1 is homologous to vertebrate Prox1, a transcription factor controlling lymphatic vessel growth. Our findings have potential evolutionary implications for the origin of fluid-collecting organs, and provide a reference for lymphangiogenesis.

PubMed

Pr08 lymphatic malformations and the molecular basis of lymphangiogenesis. Options

Pr08 lymphatic malformations and the molecular basis of lymphangiogenesis.

Options

ANZ J Surg. 2007 May

Ch'ng S, Tan ST. Wellington Regional Plastic Unit, Hutt Hospital, Wellington, New Zealand.
This paper reviews the clinical features of lymphatic malformations and the molecular basis of embryonic lymphangiogenesis.

Lymphatic malformations are classified as microcystic, macrocystic, or combined. Most commonly found in the axilla/chest and cervicofacial region, they can be localised or diffuse. The commonest complications are intralesional bleeding and infection. Other significant complications are due mainly to their mass effect on nearby anatomic structures including the airway and eyeball, and soft tissue and skeletal overgrowth including macrocheilia, macroglossia, macrotia, macromala and mandibular prognathism, resulting in functional problems in feeding, speech, occlusion, oral hygiene, and disfigurement.

The characteristic radiological finding of a LM on gadolinium-enhanced T1-weighted MRI is a low-density lesion with septation or rim enhancement. Histologically, LMs are cystic lesions that contain eosinophilic proteinaceous fluid whose walls are composed of smooth and skeletal muscle fibres, collagen and lymphocytes. Management options range from observation, comfort cares, empirical antibiotic treatment for LM cellulitis to sclerotherapy, surgical excision and Nd:YAG laser for selected cases.

Lymphangiogenesis is believed to occur in four sequential but overlapping stages: lymphatic endothelial cell competence, bias and specification, and finally lymphatic vessel terminal differentiation and maturation. Multiple genes are involved in this process including Lyve1, Nrp2, podoplanin, Prox1, VEGFR3, VEGFC and Ang2. Developmental defects during embryonic lymphangiogenesis result in lymphatic malformations.

PMID: 17490238 [PubMed - in process]

Molecular mechanisms of lymphatic vascular development.

Molecular mechanisms of lymphatic vascular development.

Cell Mol Life Sci. 2007 Apr 27

Keywords: Lymphangiogenesis - vascular remodeling - PROX1 - VEGFR-3 -FOXC2 - Ephs/ephrins

Lymphatic vasculature has recently emerged as a prominent area in biomedical research because of its essential role in the maintenance of normal fluid homeostasis and the involvement in pathogenesis of several human diseases, such as solid tumor metastasis, inflammation and lymphedema. Identification of lymphatic endothelial specific markers and regulators, such as VEGFR-3, VEGF-C/D, PROX1, podoplanin, LYVE-1, ephrinB2 and FOXC2, and the development of mouse models have laid a foundation for our understanding of the major steps controlling growth and remodeling of lymphatic vessels.

In this review we summarize recent advances in the field and discuss how this knowledge as well as use of model organisms, such as zebrafish and Xenopus, should allow further in depth analysis of the lymphatic vascular system.

Springerlink