Cdc42/N-WASP signaling links actin dynamics to pancreatic β cell delamination and differentiation.

[wiskott-aldrich syndrome]

Delamination plays a pivotal role during normal development and cancer . Previous work has demonstrated that delamination and epithelial cell movement within the plane of an epithelium are associated with a change in cellular phenotype . However , how this positional change is linked to differentiation remains unknown . Using the developing mouse pancreas as a model system , we show that β cell delamination and differentiation are two independent events , which are controlled by Cdc 42 /N-WASP signaling . Specifically , we show that expression of constitutively active Cdc 42 in β cells inhibits β cell delamination and differentiation . These processes are normally associated with junctional actin and cell-cell junction disassembly and the expression of fate-determining transcription factors , such as Isl 1 and MafA . Mechanistically , we demonstrate that genetic ablation of N-WASP in β cells expressing constitutively active Cdc 42 partially restores both delamination and β cell differentiation . These findings elucidate how junctional actin dynamics via Cdc 42 /N-WASP signaling cell-autonomously control not only epithelial delamination but also cell differentiation during mammalian organogenesis .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated