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By revealing the early commitment of these cells, we can now design more specific treatments for developmental diseases. Credit: Neuroscience News<\/p>\nSummary: Scientists have long believed that embryonic cells \u201cdecide\u201d what to become only after migrating to their final locations in the body. However, a new study has overturned this dogma.<\/p>\n
By using a \u201cmosaic barcode\u201d system to retrace the genetic history of adult cells, researchers discovered that neural crest cells, the precursors to the peripheral nervous system, are committed to their specific roles weeks earlier than previously thought, while they are still inside the embryonic neural tube.<\/p>\n
Key Findings<\/p>\n
Early Commitment: Contrary to decades of teaching, sensory ganglia (touch\/smell) and sympathetic ganglia (heartbeat\/breathing) arise from separate groups of cells before they ever leave the neural tube.Pre-Migration Identity: Most neural crest cells have already \u201cpicked their career\u201d before they peel away and migrate to different parts of the body.Orchestrated Movement: Experiments in animal models confirmed that after leaving the neural tube, these pre-committed cells spread in a strictly governed pattern to reach their target organs.Clinical Significance: This early commitment suggests that childhood cancers and nerve disorders, such as neuroblastoma or neurofibromatosis, may be rooted in events occurring much earlier in the womb than previously suspected.<\/p>\n
Source: University of Utah<\/p>\n
Millions of neurons branch throughout our bodies, keeping them in close communication with our brains. This peripheral network begins to take shape long before birth, as the cells of a growing embryo move into position and adopt their specialized roles. <\/p>\n
This crucial stage of human development can\u2019t be monitored directly, but by examining genetic clues that linger in adult cells, scientists have now gained surprising insights into the developmental origins of the peripheral nervous system.\u00a0<\/p>\n
By revealing the early commitment of these cells, we can now design more specific treatments for developmental diseases. Credit: Neuroscience News<\/p>\n
Researchers led by\u00a0Xiaoxu Yang, Ph.D.,\u00a0at\u00a0University of Utah Health\u00a0and Keng Ioi Vong, Ph.D., and Joseph Gleeson, M.D., at the University of California San Diego, have discovered that within the first few weeks of development, some of an embryo\u2019s cells have already been selected to take on particular roles in the peripheral nervous system.\u00a0<\/p>\n
Their findings, recently reported in the journal\u00a0Nature,\u00a0overturn longstanding assumptions in biology.<\/p>\n
Their discovery could change the way scientists think about treatments for a variety of childhood diseases that begin in the cells of the peripheral nervous system. \u201cBy revealing the early commitment of these cells, our study opens new avenues for research into developmental diseases and potential therapies,\u201d Yang says.\u00a0<\/p>\n
Retracing Developmental Paths<\/p>\n
As a fertilized egg transforms into an embryo, cells rapidly divide and reorganize themselves, taking on increasingly specific roles. Many of the body\u2019s tissues begin as cells called neural crest cells, which first appear in an elongated structure called the neural tube.<\/p>\n
The neural tube eventually becomes the brain and spinal cord, but many of its cells peel away and move to other parts of the developing embryo, destined to become bones, muscles, or other tissue types\u2014including the peripheral nervous system.<\/p>\n
To study this process in detail, scientists have typically turned to model organisms like mice or birds. But Gleeson and Yang knew that some important developmental events were likely to be uniquely human, so they developed a method of investigating the developmental histories of adult cells.\u00a0<\/p>\n
Their method takes advantage of the fact that although an organism\u2019s cells share a nearly identical set of genes, small changes in DNA accumulate throughout a lifetime. These changes offer clues into cells\u2019 relationships to one another.\u00a0<\/p>\n
The cells in a growing embryo multiply rapidly, with each new cell inheriting a fresh copy of the organism\u2019s DNA. The copying process is imperfect, however, and inevitably, small mutations are introduced.<\/p>\n
Once they arise, these changes\u2014most of which are harmless\u2014are passed on to new cells through future cell divisions. Not every cell inherits the same mutations, so the body is actually a mosaic of cells with subtly different sets of DNA.<\/p>\n
Gleeson, Yang, and colleagues recognized that because individual cells share patterns of mutations with the cells from which they originated, these genetic variations can serve as a barcode of shared developmental history.<\/p>\n
\u201cWe can use this mosaic barcode analysis system to really see a lot of human-specific, early developmental trajectories that nobody has seen before,\u201d Yang says.\u00a0<\/p>\n
Yang, Gleeson, and Keng Ioi Vong, a postdoctoral scholar in Gleeson\u2019s lab, used their barcode method to investigate the origins of two types of nerve clusters that lie next to the spine: sensory ganglia, which are involved in relaying sensory information like touch and smell, and sympathetic ganglia, which manage involuntary functions like breathing and heartbeat.\u00a0<\/p>\n
Redefining Histories<\/p>\n
For decades, dogma has stated that the neural crest cells that give rise to these structures take on their new identities after they migrate away from the neural tube. But the team\u2019s findings say otherwise.<\/p>\n
Their analysis of human tissues showed that the sensory and sympathetic ganglia arise from distinct groups of cells before migration, providing new insights into fundamental processes that shape the human body.\u00a0<\/p>\n
\u201cThis means that these nerve clusters have separate origins much earlier in development than previously thought,\u201d Gleeson says.\u00a0<\/p>\n
Moreover, experiments in mice and quail allowed the team to trace more developmental histories and monitor the movements of cells in developing embryos. They found that after leaving the neural tube, neural crest cells spread up and down in a carefully orchestrated pattern guided by specific signals. The sequence of events is critical for neural crest to mature into subtypes of ganglia that innervate different regions of the body.\u00a0<\/p>\n
With every experiment, the researchers gained further evidence of what they had begun to suspect: \u201cMost neural crest cells commit to their future identity before they even leave the neural tube,\u201d Vong says.<\/p>\n
Lasting Consequences<\/p>\n
Yang says the cells\u2019 early commitment to their future identities could open opportunities to develop targeted treatments for congenital nerve disorders and childhood cancers that arise from cells or tissues that originate from neural crest cells, such as neuroblastoma or neurofibromatosis.<\/p>\n
\u201cIf they\u2019re determined at a relatively early stage, we can design more specific treatments,\u201d he says.\u00a0<\/p>\n
Another implication of the work, he says, is the importance of maintaining healthy habits\u2014such as taking folic acid supplements, which can help prevent neural tube defects\u2014if there is a possibility of becoming pregnant.<\/p>\n
\u201cWe know the neural crest cells are forming a lot of very important organs and tissues in our body,\u201d he says.<\/p>\n
\u201cIf there are environmental or behavioral factors that affect this procedure, it might be affecting the final outcomes very early on.\u201d<\/p>\n
Key Questions Answered:Q: Why does it matter if a cell \u201cdecides\u201d its role a few weeks earlier?<\/p>\n
A: It changes where and when we look for the causes of birth defects and childhood cancers. If a cell is already \u201cpre-programmed\u201d in the neural tube, then environmental factors (like nutrition or toxins) might be causing damage much earlier in a pregnancy than we previously realized.<\/p>\n
Q: What is a \u201cmosaic barcode\u201d?<\/p>\n
A: It\u2019s a way of using your own DNA as a family tree for your cells. Every time a cell divides, it makes a tiny \u201ctypo\u201d (mutation). By looking at which cells in your adult body share the same \u201ctypos,\u201d scientists can prove they came from the same original \u201cparent\u201d cell in the embryo.<\/p>\n
Q: How does this discovery affect pregnancy health advice?<\/p>\n
A: It reinforces the \u201ccritical window\u201d of early development. Since these vital nerve clusters are forming their identities within the first few weeks, habits like taking folic acid are even more crucial, as the \u201cblueprint\u201d for the entire peripheral nervous system is being locked in almost immediately after conception.<\/p>\n
Editorial Notes:This article was edited by a Neuroscience News editor.Journal paper reviewed in full.Additional context added by our staff.About this neurodevelopment research news<\/p>\n
Author:\u00a0Julie Kiefer<\/a>
Source:\u00a0University of Utah<\/a>
Contact:\u00a0Julie Kiefer \u2013 University of Utah
Image:\u00a0The image is credited to Neuroscience News<\/p>\n