How MicroRNA let-7 Helps Neurons Find Their Way

2 min read

In the intricate dance of cell fate and migration within the central nervous system, a delicate balance is maintained to ensure that specific neuronal fates settle in precise spatial locations. This has been particularly evident in the mammalian neocortex, where early-born projection neurons (PNs) predominantly remain in the deeper layers of the cortical plate, whereas later-born neurons localize more superficially. However, it remains unclear whether neuronal fate acquisition directly primes the molecular mechanisms driving PN migration and positioning, or if these processes are regulated independently.

Recent studies have implicated microRNAs as key regulators of cell fate determination in the neocortex, with let-7 emerging as a crucial player in promoting the neurogenesis of late-born PNs. Notably, let-7 has been shown to influence neural progenitor competence and support the development of later-born neurons. However, its role in regulating PN migration and positioning remained unknown. Researchers Decker SC et al. have now shed light on this process by identifying a novel axis involving let-7 and RBX2.

It appears that let-7 directly binds to a conserved motif in the 3'UTR of RBX2, reducing its translation and thereby diminishing CRL5 activity. CRL5 is an E3 ubiquitin ligase that has been previously shown to inhibit neuron migration by terminating the Reelin/DAB1 signaling pathway. By targeting RBX2, let-7 effectively reduces CRL5 activity, leading to enhanced PN migration and positioning. Furthermore, restoring RBX2 levels in the context of let-7 overexpression rescues the positioning of PNs without altering let-7-induced effects on neuronal fate.

This study offers a fascinating glimpse into the complex mechanisms governing cell fate and migration within the neocortex. The identification of a novel axis involving let-7 and RBX2 highlights the intricate relationships between different molecular pathways in the development of neurons. Ultimately, this research underscores our continued fascination with the intricate workings of the brain, and invites us to ponder the broader implications of understanding these processes for our understanding of neural development and disease.

1 min read

In the intricate dance of brain development, a delicate balance of molecular signals orchestrates the migration and positioning of neurons. Specifically, the mammalian neocortex, where early-born projection neurons settle in deeper layers, and later-born neurons find their place more superficially. Yet, it remains unclear whether these processes are intertwined or independent.

Researchers have now uncovered a key player in this dance - let-7, a microRNA that influences neural progenitor competence. It promotes the neurogenesis of late-born PNs, but also regulates another crucial process: migration. The culprit behind this regulation? RBX2, a component of the E3 ubiquitin ligase CRL5.

In this study, scientists discovered that let-7 directly binds to a conserved motif in RBX2, reducing its translation and diminishing CRL5 activity. But what's remarkable is that restoring RBX2 levels in the presence of let-7 overexpression rescues the positioning of PNs without altering its effects on neuronal fate. This breakthrough sheds light on the intricate relationship between cell fate determination and migration, offering a new perspective on how our brains develop and function.

1 min read

In the intricate workings of our brains, a delicate balance is maintained between the paths that neurons take as they grow and develop. Imagine a map of the brain's pathways, carefully laid out like a puzzle. This precise arrangement ensures that specific types of nerve cells settle in specific locations.

A recent discovery sheds light on this process, revealing a key player: a tiny molecule called let-7. It helps guide the migration of these neurons to their correct spots. But what happens if this guidance is disrupted? Researchers found that by targeting a protein called RBX2, let-7 can control how neurons move and settle in place. This finding offers new insights into how our brains develop and function.