title: Pancreatic α-cell specific deletion of mouse Arx leads to α-cell identity loss.
abstract: The specification and differentiation of pancreatic endocrine cell populations (α-, β-, δ, PP- and ε-cells) is orchestrated by a combination of transcriptional regulators. In the pancreas, Aristaless-related homeobox gene (Arx) is expressed first in the endocrine progenitors and then restricted to glucagon-producing α-cells. While the functional requirement of Arx in early α-cell specification has been investigated, its role in maintaining α-cell identity has yet to be explored. To study this later role of Arx, we have generated mice in which the Arx gene has been ablated specifically in glucagon-producing α-cells. Lineage-tracing studies and immunostaining analysis for endocrine hormones demonstrate that ablation of Arx in neonatal α-cells results in an α-to-β-like conversion through an intermediate bihormonal state. Furthermore, these Arx-deficient converted cells express β-cell markers including Pdx1, MafA, and Glut2. Surprisingly, short-term ablation of Arx in adult mice does not result in a similar α-to-β-like conversion. Taken together, these findings reveal a potential temporal requirement for Arx in maintaining α-cell identity.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Wilcox
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Terry
authors.forename: Erik R
authors.initials: ER
authors.lastname: Walp
authors.forename: Randall A
authors.initials: RA
authors.lastname: Lee
authors.forename: Catherine Lee
authors.initials: CL
authors.lastname: May
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C469265:ARX protein, mouse; D015415:Biomarkers; D018398:Homeodomain Proteins; D007328:Insulin; D014157:Transcription Factors; D005934:Glucagon