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Lethal Alleles

Lethal Alleles

Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...

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Hyperactive Rac converts sublethal to lethal trogocytosis in vivo.

Lauren Penfield¹, Abhinava K Mishra^1,2, Morgan Smith¹

¹Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, CA 93106.

Proceedings of the National Academy of Sciences of the United States of America

|April 6, 2026

Summary

This summary is machine-generated.

Hyperactivated Rac signaling in Drosophila border cells triggers lethal cannibalism of nurse cells. This study reveals mechanisms of cell killing and engulfment, with implications for cancer therapies.

Keywords:

CAR-M Drosophila ovary phagocytosis trogocytosis

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Area of Science:

Cell Biology
Developmental Biology
Molecular Biology

Background:

The small GTPase Rac is crucial for cell shape, migration, and phagocytosis.
Constitutively active Rac (Rac^G12V) induces cannibalism in Drosophila border cells.

Purpose of the Study:

Investigate mechanisms of border cell-mediated killing of nurse cells.
Elucidate the roles of Rac and Draper in trogocytosis.

Main Methods:

Drosophila melanogaster model system.
Clonal analysis of Rac^G12V expression.
Assessing cell death markers (caspase activation, nuclear damage).

Main Results:

Rac^G12V causes lethal 'bites' leading to nurse cell death and engulfment by follicle cells.
Rac and Draper are essential for both sublethal and lethal trogocytosis.
Rac-independent germline death can be induced by increased Draper or JNK activity.

Conclusions:

Hyperactivated Rac in few cells can trigger destruction of a larger cell mass.
Multiple pathways can activate border cells for killing.
Findings inform the development of cancer-engulfing therapies (RaceCAR-Ms).