Perfect timing: Making the 'switch' from juvenile to adult

July 03, 2019

Very little is known about how the onset of puberty is controlled in humans, but the discovery of a new gene in the roundworm C. elegans could be the "missing link" that determines when it's time to make this juvenile-to-adult transition. Two genes, LIN28 and MKRN3, are known to be associated with precocious puberty in humans, where juveniles as young as six may start developing adult features. These genes are found in all animals, including C. elegans, in which they also control the juvenile-to-adult transition. Until the new discovery, it was unclear how these two genes are connected.

The more obvious signs of the transition of juvenile-to-adult tend to be external--body morphology, matured genitalia--but nervous system changes are also happening at the same time. In humans, the maturation of the brain during adolescence is associated with increased vulnerability to a variety of neuropsychiatric disorders, so a better understanding of these processes is important for understanding mental health as well as basic neurobiology.

Two new studies in the labs of Douglas Portman, Ph.D. at the University of Rochester Medical Center and David Fitch at New York University, published in Developmental Cell and eLife, identified a new developmental timing mechanism involving a long non-coding RNA in the microscopic roundworm C. elegans. Their research revealed a surprising new molecular mechanism that controls the timing of sex-specific changes in body shape, the maturation of neural circuits, and behavior.

C. elegans has long been used by researchers to understand fundamental mechanisms in biology. Many of the discoveries made using these worms apply throughout the animal kingdom and this research has led to a broader understanding of human biology. In fact, three Nobel Prizes in medicine and chemistry have been awarded for discoveries involving C. elegans.

The researchers identified a new gene that, when disrupted, delays the transition from the juvenile to the adult stage. Surprisingly, this gene, called lep-5, does not act as a protein, as most genes do. Instead, it functions as a long non-coding RNA (lncRNA), a recently discovered class of genes whose functions remain largely mysterious. The team observed that this lncRNA is important for promoting the juvenile-to-adult transition by directly interacting with LIN-28 and LEP-2, a C. elegans gene similar to MKRN3. Because the human versions of LEP-2 and LIN-28 are both involved in the timing of puberty, the new research suggests that a yet-to-be-discovered lncRNA might be essential to this process in humans as well.

In the roundworm nervous system, some neural circuits undergo a functional transition in males as they become sexually mature adults, which is critical for generating adult-specific behaviors important for reproductive success. The male tail also undergoes a change in shape that enables mating behavior. The researchers found that this same pathway controls both the functional maturation of these circuits and the shape of the tail. Roundworms carrying mutations in lep-5 become physically mature adults, but their nervous system remains arrested in the juvenile stage, and their tails retain a juvenile form.

With respect to changes in behavior, the pathway regulates this timing by acting in the nervous system itself, not in a tissue that sends timing signals to the nervous system. Moreover, individual neurons manage their own developmental clocks. A timed "pulse" of lep-5 activity during the juvenile stage causes LIN-28 to become inactive, allowing the transition to adulthood to proceed.

Continued studies of the mechanisms identified in these studies will help scientists better understand the ways in which genetic and environmental cues regulate the transition to adulthood in humans. This research was supported by the National Institute of General Medical Sciences and National Science Foundation grants to Portman and Fitch.
-end-


University of Rochester Medical Center

Related Nervous System Articles from Brightsurf:

Chikungunya may affect central nervous system as well as joints and lungs
Investigation conducted by international group of researchers showed that chikungunya virus can cause neurological infections.

Glial cells play an active role in the nervous system
Researchers at M√ľnster University, Germany, have discovered that glial cells - one of the main components of the brain -not only control the speed of nerve conduction, but also influence the precision of signal transduction in the brain.

Protein produced by the nervous system may help treatments for inflammatory diseases
A Rutgers-led team discover a protein produced by nervous system may be key to treating inflammatory diseases like asthma, allergies, chronic fibrosis and chronic obstructive pulmonary disease (COPD)

COVID-19 may attack patients' central nervous system
''There may be more central nervous system penetration of the virus than we think based on the prevalence of olfaction-associated depressed mood and anxiety and this really opens up doors for future investigations to look at how the virus may interact with the central nervous system,'' explains Ahmad Sedaghat, MD, PhD.

Lifting weights makes your nervous system stronger, too
Gym-goers may get frustrated when they don't see results from weightlifting right away, but their efforts are not in vain: the first few weeks of training strengthen the nervous system, not muscles.

COVID-19 threatens the entire nervous system
A new review of neurological symptoms of COVID-19 patients in current scientific literature reveals the disease poses a global threat to the entire nervous system.

Fewer scars in the central nervous system
Researchers have discovered the influence of the coagulation factor fibrinogen on the damaged brain.

Polymerized estrogen shown to protect nervous system cells
In research published today in Nature Communications, an interdisciplinary team from Rensselaer Polytechnic Institute demonstrated how estrogen -- a natural hormone produced in the body -- can be polymerized into a slow-releasing biomaterial and applied to nervous system cells to protect those cells and even promote regeneration.

Discovery concerning the nervous system overturns a previous theory
It appears that when our nervous system is developing, only the most viable neurons survive, while immature neurons are weeded out and die.

Autonomic nervous system appears to function well regardless of mode of childbirth
'In a low-risk group of babies born full-term, the autonomic nervous system and cortical systems appear to function well regardless of whether infants were exposed to labor prior to birth,' says Sarah B.

Read More: Nervous System News and Nervous System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.