A Key Cytoskeletal Regulator of Ubiquitination Amplifies TGFβ Signaling during Mouse Developmental Vascular Patterning

BioRxiv : the Preprint Server for Biology
Ronak ShettyManeesha S Inamdar

Abstract

Vascular development involves de novo formation of a capillary plexus, which is then pruned and remodeled by angiogenic events. Cytoskeletal remodeling and directional endothelial migration are essential for developmental and pathological angiogenesis. Smad-dependent TGFβ signaling controls vascular patterning and is negatively regulated by microtubules. Here we show that a positive regulator of TGFβ signaling is essential for developmental vascular patterning and microtubule stability. Rudhira/BCAS3 is known to bind microtubules and to play a nodal role in cytoskeletal remodeling and directional endothelial cell (EC) migration in vitro. We demonstrate that the molecular and cellular function of Rudhira is deployed at critical steps in vascular patterning. We generated the first floxed mice for rudhira and find that global or endothelial knockout of rudhira results in mid-gestation lethality due to aberrant embryonic and extra-embryonic vessel patterning and defective cardiac morphogenesis. Rudhira null yolk sac ECs show random and retarded migration. Yolk sac transcriptome analysis revealed key mediators of angiogenic processes and TGFβ receptor signaling were perturbed in rudhira null mutants. Molecular and biochemical analys...Continue Reading

Related Concepts

Embryo
Study
Biochemical Pathway
Transforming Growth Factor beta
TGFA protein, human
Gene Amplification
Angiogenic Process
Blood Vessel
Knock-out
Inhibitors

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.