Mesenchymal transcription factor Fkh6 is essential for the development anddifferentiation of parietal cells

The role of transcription factor forkhead homologue 6 (Fkh6) gene expressed only in gastrointestinal mesenchymes on the differentiation of gastric epi thelia was analyzed by inactivating the gene by targeting disruption. Gastr ic mucosa exhibited hyperplasias with disordered glandular structures in th e absence of gene. Measurement of acid secretion in the isolated whole stom ach demonstrated that both basal and stimulated secretions were severely su ppressed in the Fkh6-/- stomach, while immunohistochemical studies showed t hat comparable numbers of parietal cells were differentiated in both wild-t ype and Fhh6-/- stomachs. Ultrastructurally Fkh6-/- parietal cells were fur nished with developed intracellular canaliculi and many mitochondria, but t heir canaluculi were not enlarged nor fully connected to the luminal surfac e even when animals were treated with histamine, suggesting that Fkh6-/- pa rietal cells were far less responsive to acid secretion-inducing stimulatio ns. Some parietal cells contained secretory granules positively stained wit h anti-pepsinogen antibodies, indicating that they retained characteristics of oxynticopeptic cells found in lower vertebrates. We thus concluded that Fkh6 plays essential roles for the development and differentiation of pari etal cells via epithelial-mesenchymal interactions. (C) 2001 Academic Press .