Prox1 activity controls pancreas morphogenesis and participates in the production of "secondary transition" pancreatic endocrine cells


Wang J., Kılıç G., Aydin M. , Burke Z., Olıver G., Sosa-Pıneda B.

DEVELOPMENTAL BIOLOGY, cilt.286, ss.182-194, 2005 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 286
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1016/j.ydbio.2005.07.021
  • Dergi Adı: DEVELOPMENTAL BIOLOGY
  • Sayfa Sayıları: ss.182-194

Özet

The development of the mammalian pancreas is governed by various signaling processes and by a cascade of gene activation events controlled by different transcription factors. Here we show that the divergent homeodomain transcription factor Proxl is a novel, crucial regulator of mouse pancreas organogenesis. Loss of Proxl function severely disrupted epithelial pancreas morphology and hindered pancreatic growth without affecting significantly the genesis of endocrine cells before E11.5. Conversely, the lack of Proxl activity substantially decreased the formation of islet cell precursors after E13.5, during a period known as the "secondary transition". Notably, this defect occurred concurrently with an abnormal increment of exocrine cells. Hence, it is possible that Proxl contributes to the allocation of an adequate supply of islet cells throughout pancreas ontogeny by preventing exocrine cell differentiation of multipotent pancreatic progenitors. Proxl thus appears to be an essential component of a genetic program destined to produce the cellular complexity of the mammalian pancreas. (c) 2005 Elsevier Inc. All rights reserved.

The development of the mammalian pancreas is governed by various signaling processes and by a cascade of gene activation events controlled by different transcription factors. Here we show that the divergent homeodomain transcription factor Proxl is a novel, crucial regulator of mouse pancreas organogenesis. Loss of Proxl function severely disrupted epithelial pancreas morphology and hindered pancreatic growth without affecting significantly the genesis of endocrine cells before E11.5. Conversely, the lack of Proxl activity substantially decreased the formation of islet cell precursors after E13.5, during a period known as the "secondary transition". Notably, this defect occurred concurrently with an abnormal increment of exocrine cells. Hence, it is possible that Proxl contributes to the allocation of an adequate supply of islet cells throughout pancreas ontogeny by preventing exocrine cell differentiation of multipotent pancreatic progenitors. Proxl thus appears to be an essential component of a genetic program destined to produce the cellular complexity of the mammalian pancreas.