[HTML][HTML] A fork in the road of cell differentiation in the kidney tubule

Q Al-Awqati, GJ Schwartz - The Journal of clinical …, 2004 - Am Soc Clin Investig
Q Al-Awqati, GJ Schwartz
The Journal of clinical investigation, 2004Am Soc Clin Investig
The collecting ducts of the kidney are composed of intercalated cells (responsible for
acid/base transport), principal cells (mediating salt and water absorption), and inner
medullary cells, which mediate all three types of transport. Forkhead box (Fox) genes are a
large family of transcription factors that are important in cell-type specification during
organogenesis. In this issue, Blomqvist et al. find that mice lacking Foxi1 have no
intercalated cells in the kidney. The collecting ducts of the null mice contained primitive cells …
The collecting ducts of the kidney are composed of intercalated cells (responsible for acid/base transport), principal cells (mediating salt and water absorption), and inner medullary cells, which mediate all three types of transport. Forkhead box (Fox) genes are a large family of transcription factors that are important in cell-type specification during organogenesis. In this issue, Blomqvist et al. find that mice lacking Foxi1 have no intercalated cells in the kidney. The collecting ducts of the null mice contained primitive cells that expressed both intercalated cell and principal cell proteins, yet the acid/base transport function of the kidney was disrupted and the mice exhibited distal renal tubular acidosis. These findings suggest that Foxi1 plays a critical role in determining cell identity during collecting duct development.
The mechanism of generation of the 400 or more cell types of mammals from a single cell remains the principal problem of developmental cell biology. Classical embryologists discovered that progenitor cells first undergo specification before they become determined to form a differentiated cell type. Under certain conditions, specified cells can differentiate in a reversible manner, whereas determined cells autonomously differentiate even if placed in a different location in the embryo. The molecular mechanism of these changes in cell fate depends on signals received from the niche or “ecosystem” in which the cell is located, but ultimately it must involve the activation of a network of transcription factors that is specific for each tissue and cell type.
The Journal of Clinical Investigation