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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
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Developmental Biology - Cell Structure

What Signals Muscle Cell Differentiation?

Novel genes are responsible for regulating muscle cells...

At York University in Toronto, Canada, scientists have uncovered a unique set of genes in muscle gene expression and differentiation which could lead to new therapeutic targets preventing muscle cancer spread.

Published in the journal Cell Death & Disease, the study indicates how a dysfunctional relationship between Smad7 and -catenin can lead to impaired muscle cell differentiation a hallmark of some soft tissue cancers such as Rhabdomyosarcoma (RMS). This rare cancer most often affects children and forms in soft, mostly skeletal muscle tissue, although sometimes in hollow organs like the bladder or uterus.

Regulatory proteins Smad7 and -catenin cooperatively regulate muscle cell differentiation, growth, and repair. When working in harmony,
their control of signalling pathways of gene expression results in normal skeletal muscle cells.

"What happens in rhabdomyosarcoma cells is that normal muscle cells cannot stop dividing," explains John McDermott, professor, department of Biology at York University, Toronto, who supervised the study and is a contributing author. Although these cells look like muscle cells, in terms of function and phenotype, their inability to stop dividing forms tumors.
"Our idea is that part of the reason why those cells are defective...is that the -catenin complex is being degraded...because of an anomaly in the signaling pathway. If we can stabilize the -catenin and Smad7 complex...you could potentially encourage them to differentiate and stop proliferating...you'd stop those cells from growing in the tumor."

John C. McDermott PhD, Department of Biology, York University, Toronto, Canada; Muscle Health Research Centre (MHRC); Centre for Research in Biomolecular Interactions (CRBI); and Centre for Research in Mass Spectrometry (CRMS), York University, Toronto, ON, Canada.

Research conducted in York's Muscle Health Research Centre, the first of its kind in Canada, focuses on skeletal muscle. With this new finding, it will also open up new molecular targets for interventions in muscle wasting, leading to strategies for cancer treatments targeting these specific molecules.

By identifying the role of DNA binding proteins, the team also opens possible new regulators of muscle regeneration and avenues for treating the loss of muscle in aging.
"Muscle regeneration is complex and regulated by a variety of transcription factors essential proteins that help turn genes on or off by binding to specific ones. We believe two such transcription factors, Smad7 and -catenin, play a key role in the specific pattern of gene expression required for muscle development and repair."

Soma Tripathi PhD, Department of Biology, York University, Toronto, Canada; Muscle Health Research Centre (MHRC); Centre for Research in Biomolecular Interactions (CRBI); and Centre for Research in Mass Spectrometry (CRMS), York University, Toronto, ON, Canada.

Recent reports indicate that Smad7 promotes skeletal muscle differentiation and growth. We previously documented a non-canonical role of nuclear Smad7 during myogenesis, independent of its role in TGF-? signaling. Here further characterization of the myogenic function of Smad7 revealed -catenin as a Smad7 interacting protein. Biochemical analysis identified a Smad7 interaction domain (SID) between aa575 and aa683 of -catenin. Reporter gene analysis and chromatin immunoprecipitation demonstrated that Smad7 and -catenin are cooperatively recruited to the extensively characterized ckm promoter proximal region to facilitate its muscle restricted transcriptional activation in myogenic cells. Depletion of endogenous Smad7 and -catenin in muscle cells reduced ckm promoter activity indicating their role during myogenesis. Deletion of the -catenin SID substantially reduced the effect of Smad7 on the ckm promoter and exogenous expression of SID abolished -catenin function, indicating that SID functions as a trans dominant-negative regulator of -catenin activity. -catenin interaction with the Mediator kinase complex through its Med12 subunit led us to identify MED13 as an additional Smad7-binding partner. Collectively, these studies document a novel function of a Smad7-MED12/13--catenin complex at the ckm locus, indicating a key role of this complex in the program of myogenic gene expression underlying skeletal muscle development and regeneration.

Soma Tripathi, Tetsuaki Miyake and John C. McDermott.

This work was supported by the Canadian Institutes of Health Research (102688 to J.C.M.). J.C.M. is supported by the McLaughlin Research Chair, York University.

York University champions new ways of thinking that drive teaching and research excellence. Our students receive the education they need to create big ideas that make an impact on the world. Meaningful and sometimes unexpected careers result from cross-disciplinary programming, innovative course design and diverse experiential learning opportunities. York students and graduates push limits, achieve goals and find solutions to the world's most pressing social challenges, empowered by a strong community that opens minds. York U is an internationally recognized research university - our 11 faculties and 25 research centres have partnerships with 200+ leading universities worldwide. Located in Toronto, York is the third largest university in Canada, with a strong community of 53,000 students, 7,000 faculty and administrative staff, and more than 300,000 alumni.

York U's fully bilingual Glendon Campus is home to Southern Ontario's Centre of Excellence for French Language and Bilingual Postsecondary Education.

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May 30 2019   Fetal Timeline   Maternal Timeline   News  

Muscle tissue cells.

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