One of the most dramatic phases of fetal development occurs as previously unstructured collections of rapidly dividing precursor cells begin forming the embryo’s spine.
When this process goes well, it sets a solid foundation for the many other development steps that follow. When it does not, the growth defects that follow can be severe.
Now, a research team has discovered how a set of segmentation clock genes instruct the tempo of spine formation. Mutations of clock genes lead to birth defects in humans called congenital scoliosis. The team’s findings open doors wider to a new wave of basic science research that may someday allow interventions when clock genes throughout our bodies fall out-of-sync.
Details were published in the journal Nature.
In animals with spines (including humans), the growing embryo forms soft segments called somites that later form into bony vertebrae. These somites also give rise to rib formation and related back muscles and skin.
A research team identified a dip in molecular cell signaling that prompts the formation of a new segment. The work involved using zebrafish with gene modifications to detect key signaling variations. By using what they learned about the signaling, the research team was able to biochemically induce segment formation in zebrafish at will even though the fish had been engineered to lack the clock genes that normally control this process.
The latest work builds on widely shared findings from the team about how co-expressed gene pairs help drive the timing of body segmentation.
“We think this study will be important for researchers in biology, bioengineering, and computational biology,” the senior author says. “Understanding how cells are primed to form a segment boundary at a specific location could help researchers understand the origins of other malformations that can occur during fetal development in addition to early spine formation.”
The team confirmed that the signaling molecules they studied are conserved from fish to humans. However, it will require much more research to determine if the interventions that helped correct spine malformations in the zebrafish can be translated to humans.
One hopeful longer-term application of this study may be that it provides guidance for attempting to grow segmented tissues (like the spine and digits in the hand) in the lab, suggesting a new front for organoid development.
“Broad animal species from centipedes and beetles to humans segment their body sequentially. While the molecules involved diverge dramatically among species, our study indicated that sequential segmentation can still be achieved as long as a clock stamps its periodicity on a morphogen gradient,” the author says. “We anticipate our findings will inspire engineering repetitively organized tissues in dish by utilizing pulsatile perturbation of signaling gradients.”
The next step is to discover the molecular link between the segmentation clock and its downstream signaling pathway.
“We are hopeful that discovering the so-far missing molecular link could be clinically relevant and targetable,” the author says.
https://www.nature.com/articles/s41586-022-05527-x
Spine development without segmentation clocks
- 1,157 views
- Added
Edited
Latest News
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Addressing both flu and COV…
By newseditor
Posted 26 Mar
How the brain senses body p…
By newseditor
Posted 26 Mar
Other Top Stories
Trigger for Alzheimer's disease found!
Read more
People with anxiety show fundamental differences in perception
Read more
Genetically elevated 'good' cholesterol may actually be bad
Read more
Yoga improves quality of life in patients with atrial fibrillation
Read more
Protecting against oxidative damage and improving healthspan
Read more
Protocols
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Profiling native pulmonary…
By newseditor
Posted 08 Mar
Publications
Balancing neuronal activity…
By newseditor
Posted 28 Mar
OSBP-mediated PI(4)P-choles…
By newseditor
Posted 28 Mar
Integrated plasma proteomic…
By newseditor
Posted 27 Mar
APP antisense oligonucleoti…
By newseditor
Posted 27 Mar
Targeting Erbin-mitochondri…
By newseditor
Posted 27 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar