Calreticulin Deficiency Disturbs Ribosome Biogenesis and Results in Retardation in Embryonic Kidney Development

Area of Science:

• Developmental Biology
• Molecular Biology
• Biochemistry

Background:

• Nephrogenesis, the formation of kidneys, involves intricate signaling pathways controlling cell growth and differentiation.
• Calreticulin (Calr), an endoplasmic reticulum chaperone, is known for calcium storage and glycoprotein folding, but its role in kidney development is unclear.

Purpose of the Study:

• To investigate the role of Calreticulin (Calr) in mammalian kidney development (nephrogenesis).
• To elucidate the molecular mechanisms underlying Calr's function in embryonic kidney formation.

Main Methods:

• Utilized Calreticulin-deficient (Calr-/-) mouse models.
• Employed proteomics and transcriptomics to analyze gene and protein expression.
• Confirmed findings using CRISPR/cas9 mediated knockout.

Main Results:

• Calr deficiency led to disrupted nephrogenic zone formation and retarded nephrogenesis, evidenced by abnormal comma- and s-shaped body development.
• Proteomics and transcriptomics revealed impaired Wnt-signaling and reduced expression of ribosomal proteins in Calr-/- kidneys, indicating compromised protein synthesis.
• CRISPR/cas9 confirmed Calr deficiency's link to deficiencies in ribosomal proteins and ribosome biogenesis.

Conclusions:

• Calreticulin plays a critical role in regulating nephrogenesis.
• Calr deficiency impairs kidney development by disrupting ribosome biogenesis and protein synthesis.
• A direct link exists between Calreticulin expression and ribosome biogenesis during kidney development.