Welcome to The Visible Embryo
The Visible Embryo Birth Spiral Navigation
Fetal Timeline--- -Maternal Timeline-----News-----Prescription Drugs in Pregnancy---- Pregnancy Calculator----Female Reproductive System

WHO International Clinical Trials Registry Platform

The World Health Organization (WHO) has a Web site to help researchers, doctors and patients obtain information on clinical trials.

Now you can search all such registers to identify clinical trial research around the world!




Pregnancy Timeline

Prescription Drug Effects on Pregnancy

Pregnancy Calculator

Female Reproductive System


Disclaimer: The Visible Embryo web site is provided for your general information only. The information contained on this site should not be treated as a substitute for medical, legal or other professional advice. Neither is The Visible Embryo responsible or liable for the contents of any websites of third parties which are listed on this site.

Content protected under a Creative Commons License.
No dirivative works may be made or used for commercial purposes.


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


Ryk needs a chaperone

Ryk and Smek are two proteins responsible for development of the fetal brain cortex...

Ryk is featured in a new study published in the Proceedings of the National Academy of the Sciences (PNAS).

In the study, first authors Wen-Hsuan Chang PhD of the The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, at the University of Southern California, (USC) Los Angeles, along with Wange Lu PhD, and Si Ho Choi PhD also of the Dongnam Institute of Radiological & Medical Sciences (DIRAMS) in South Korea, describe how Ryk and its chaperones, Smek1 and Smek2, contribute to the development of the fetal brain cortex the gray matter responsible for our consciousness.

During cortical development, a part of Ryk called the intracellular domain (ICD) must be chaperoned into the stem cell nucleus to assist in its conversion into neurons. Chang's team discovered that the Ryk chaperone is a protein named Smek. Smek not only chaperones Ryk into the nucleus, which contains the stem cell's genes, Smek also works with Ryk to regulate the activity of key genes that transform stem cells into brain cells.
"Such studies not only help us understand the mechanisms of how stem cells become neurons, but also will become useful for us in developing therapies to treat neurological diseases including brain cancers."

Wange Lu, Associate Professor, Stem Cell Biology and Regenerative Medicine, Biochemistry and Molecular Biology.

Receptor-like tyrosine kinase (Ryk) is a Wnt receptor and is important for many developmental processes, including cranial facial development, neurogenesis, and axon guidance. However, little is known about the role of the intracellular domain, Ryk-ICD, in signal transduction. Its downstream targets are also unknown. We have previously shown that Ryk-ICD is located in the cytoplasm of neural stem cells whereas it moves into the nucleus upon neuronal differentiation. In this study, we discovered that Smek1/2 function as a chaperone for Ryk-ICD during its nuclear localization and that both Smek and Ryk-ICD associate with chromatin to regulate the transcription of downstream target genes and neural differentiation.

The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell fate determination during corticogenesis. During neuronal differentiation, the Ryk intracellular domain (ICD) is cleaved. Cleavage of Ryk and nuclear translocation of Ryk-ICD are required for neuronal differentiation. However, the mechanism of translocation and how it regulates neuronal differentiation remain unclear. Here, we identified Smek1 and Smek2 as Ryk-ICD partners that regulate its nuclear localization and function together with Ryk-ICD in the nucleus through chromatin recruitment and gene transcription regulation. Smek1/2 double knockout mice displayed pronounced defects in the production of cortical neurons, especially interneurons, while the neural stem cell population increased. In addition, both Smek and Ryk-ICD bound to the Dlx1/2 intergenic regulator element and were involved in its transcriptional regulation. These findings demonstrate a mechanism of the Ryk signaling pathway in which Smek1/2 and Ryk-ICD work together to mediate neural cell fate during corticogenesis.

Additional authors include: Byoungsan Moon, Mingyang Cai, Jinlun Bai, Fan Gao, Ibrahim Hajjali, Daniel Campbell, and Leslie Weiner from USC; Jungmook Lyu from Konyang University in South Korea; and Zhongfang Zhao from Nankai University in China.

Ninety-five percent of this work was supported by $1,727,898 in U.S. federal funding from a National Institutes of Health grant (R01 NS067213-01A1). Five percent of the project was funded by $10,000 from two non-U.S. sources: a DIRAMS grant funded by the South Korean government (50590-2017), and the National Natural Science Foundation of China.

Return to top of page

Nov 29, 2017   Fetal Timeline   Maternal Timeline   News   News Archive

Embryonic mouse cortex with neural stem cells (red) and neurons (green). Timing: approximately Carnegie Stage 13. Image credit: Wen-Hsuan Chang of the Wange Lu Lab, University of Southern California.

Phospholid by Wikipedia