Stum-KO Mouse

Stum, or stumble, is an evolutionarily conserved gene essential for mechanical sensing in a specific subpopulation of Drosophila proprioceptive neurons that sense joint angles. The Stum protein has orthologs in animals from nematodes to mammals and is predicted to contain two transmembrane domains [1]. These neurons expressing Stum are crucial for animal locomotion as they generate proprioceptive feedback [1,3].

A genetic screen in Drosophila identified stum as a gene involved in mechanical transduction in leg joint proprioceptive neurons [1,3]. In these neurons, the dendrites are stretched by joint movements, leading to elevation of cellular Ca(2+) levels, which is absent in stum mutants [1]. Also, stum -expressing neurons express the mechanosensory channel NOMPC, and in nompC mutants, responses to joint position are abolished, indicating that NOMPC is the mechanosensitive channel in these neurons [3]. Additionally, a mutant initially thought to affect stum was later found to be a new allele of O -fucosyltransferase 1, acting through the Notch signaling pathway upstream of the S2 cleavage of the Notch receptor in Drosophila intestinal stem cell regulation [2].

In conclusion, Stum is vital for mechanical sensing in proprioceptive neurons, contributing to animal locomotion. The study of Stum in Drosophila models has revealed its role in mechanotransduction and potential connections to other signaling pathways like Notch, enhancing our understanding of the underlying biological processes related to proprioception and stem cell regulation.

References:

1. Desai, Bela S, Chadha, Abhishek, Cook, Boaz. . The stum gene is essential for mechanical sensing in proprioceptive neurons. In Science (New York, N.Y.), 343, 1256-9. doi:10.1126/science.1247761. https://pubmed.ncbi.nlm.nih.gov/24626929/

2. Shi, Lin, Kong, Ruiyan, Li, Zhengran, Li, Jing, Li, Zhouhua. 2021. Identification of a new allele of O-fucosyltransferase 1 involved in Drosophila intestinal stem cell regulation. In Biology open, 10, . doi:10.1242/bio.058910. https://pubmed.ncbi.nlm.nih.gov/34731235/

3. Chadha, Abhishek, Kaneko, Maki, Cook, Boaz. 2015. NOMPC-dependent mechanotransduction shapes the dendrite of proprioceptive neurons. In Neuroscience letters, 597, 111-6. doi:10.1016/j.neulet.2015.04.033. https://pubmed.ncbi.nlm.nih.gov/25916878/