H-Ras, R-Ras, and TC21 differentially regulate ureteric bud cell branching morphogenesis

Area of Science:

• Developmental Biology
• Cell Biology
• Molecular Biology

Background:

• The kidney's collecting system develops through branching morphogenesis, a process crucial for kidney function.
• Ras GTPase family members regulate cell growth, differentiation, proliferation, and migration, but their specific roles in kidney collecting system development are unknown.

Purpose of the Study:

• To investigate the roles of R-Ras, TC21, and H-Ras in the development of the murine kidney collecting system.

Main Methods:

• Expression analysis of R-Ras, TC21, and H-Ras in murine collecting systems at different developmental stages (E13.5 and E17.5).
• Functional analysis using murine ureteric bud (UB) cells expressing activated forms of H-Ras, R-Ras, and TC21 to assess effects on branching morphogenesis and cell migration.
• Analysis of downstream signaling pathways, including Rho family GTPases and mitogen-activated protein kinases.

Main Results:

• R-Ras and TC21 are expressed in the early collecting system (E13.5), while H-Ras expression is detected later (E17.5).
• R-Ras expression increased branching morphogenesis and cell growth.
• TC21 expression led to excessive branching but impaired migration.
• H-Ras expression promoted cell migration and formation of long, unbranched tubules.
• Differential activation of Rho GTPases and MAP kinases mediated these distinct cellular behaviors.

Conclusions:

• R-Ras and TC21 likely facilitate early branching and growth of the ureteric bud during kidney development.
• H-Ras may play a role in later developmental events, such as cell migration and tubule elongation.