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The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

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Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development




 

How genes link heart and neurodevelopmental disease

Harvard medical research shows children with both congenital heart disease and neurodevelopmental delays share genetic mutations.


Children with significant congenital heart disease have a far better chance of surviving today than in decades past, thanks to major advances in surgery. But some infants who recover from repairs to their hearts later show the effects of delays in brain development, including impairments to cognitive, language and social functioning. These impairments can affect how well these children do in school and in the workplace; they can even diminish their overall quality of life.


Epidemiologic research has attached numbers to what doctors and families have long observed: The risk of neurodevelopmental delays is tenfold higher for children with moderate to severe congenital heart disease than for other children. But why?


Over the years, those who study these phenomena have considered several possible reasons. Do the rigors of open-heart surgery so soon after birth play a role? Could heart defects limit nutrients and oxygen needed by the fetus? Or could spontaneous genetic mutations cause congenital problems that affect both the heart and the brain of a child?

Now, the 'why' may have been answered by the efforts of the Pediatric Cardiovascular Genetics Consortium, led by a team of Harvard Medical School scientists. In a recent issue of Science the consortium reported the analysis of exome sequences of more than 1,200 children and their parents. This process showed that children with both congenital heart disease and neurodevelopmental delays share certain genetic mutations that stop normal development in both the heart and brain.

The research team used a mathematical model created by co-authors Kaitlin Samocha PhD and Mark Daly PhD, of the Analytical and Translational Genetics Unit at Massachusetts General Hospital and Harvard Medical School, Boston MA, USA. Samocha and Daly analyzed mutations in the protein-coding portion of the genomes of children with congenital heart disease — that were not present in their parents' genomes. These children had more new mutations in genes highly expressed in their developing hearts as compared to a control cohort of children without congenital heart disease.

The de novo mutations were also found more frequently in children with congenital heart disease plus another birth defect, either neurodevelopmental delay or more-subtle abnormalities in finger or ear shape. These findings bolster the case for a shared genetic cause of cardiac and extra-cardiac abnormalities rather than causes from surgeries or environmental factors.


"We're homing in on a set of genes that have multiple different roles in multiple different tissues during development: heart tissue, brain tissue, other developing organs, limb tissue. Our study shows a common genetic link for the development of these diseases."

Jason Homsy, HMS LaDue Fellow, trained at Mass General, co-lead author of the Science paper.


According to Homsy and co-senior author Christine Seidman PhD, HMS Thomas W. Smith Professor of Genetics and Medicine at Brigham and Women's Hospital and a Howard Hughes Medical Institute investigator, these findings could lead to early testing that would help identify newborns with congenital heart disease and at high risk for neurodevelopmental difficulties.

"We can pretty clearly tell the parents of children with congenital heart disease what's going to happen after the heart surgery, but there's always a big question: Will my kid learn well in school?" Seidman said. "If we could identify children at high risk for neurodevelopmental delays, they could receive increased surveillance and earlier interventions than occur now."


Mutations primarily affected genes in three areas:
(1) morphogenesis: origin of morphological differences in organs
(2) chromatin modification: alterating DNA, protein, and RNA, which make up chromosomes
(3) regulation of transcription:regulating how DNA is copied into messenger RNA (mRNA)

If any one of these processes is perturbed even slightly at a critical time in development, the heart is malformed. Sometimes another developmental defect occurs, such as a missed connection in the brain.


"These genes are not just involved in shaping the heart," Seidman adds, "They are master regulators of organ development."

One of the mutated genes is RBFOX2. RBFOX2 encodes a molecule that regulates RNA splicing. Although it had not previously been implicated in congenital heart disease, fresh or new mutations were identified in multiple affected children.

Seidman: "There are still many unanswered questions, including why the same mutation can cause very different clinical manifestations. It's a long, long, long way down the road, but we'd like to believe that if you knew the steps by which these mutations perturb regulation of gene expression, there might even be ways to actually treat that perturbation."

Acccording to Seidman, knowing that a genetic mutation is present is different from knowing its outcome. Perhaps additional genetic variations within the multiple layers of transcription regulation allow for compensation by some mutations, but worsen the consequences of others.

Abstract
Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2% of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator of mRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients.

This work was supported by grants from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute of the National Institutes of Health, Howard Hughes Medical Institute, Simons Foundation for Autism Research, John S. LaDue Fellowship at HMS, Medical Scientist Training Program and National Research Science Award, Academy of Medical Sciences, British Heart Foundation, Wellcome Trust, Arthritis Research UK and the NIHR Cardiovascular Biomedical Research Unit at Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, Leducq Foundation, Heart and Stroke Foundation of Ontario, Ted Rogers Centre for Heart Research, Kostin Family Innovation Fund, Aaron Stern Professorship at the University of Michigan, and Braylon's Gift of Hope Fund.

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Dec 28, 2015   Fetal Timeline   Maternal Timeline   News   News Archive   



Splicing is needed in messenger RNA (mRNA) to produce the correct protein. 
Splicing is also how pre-mRNA is modified. In pre-messenger RNA transcription,
which is when a segment of DNA is copied into RNA (mRNA) by an enzyme called
RNA polymerase, introns are removed and exons are joined.
Image Credit: Wikipedia




 





 


 

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