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* At the beginning of the fourth week, folding in the median and horizontal planes converts the flat trilaminar embryonic disc into a C-shaped, cylindrical embryo. The formation of the head, caudal eminence, and lateral folds is a continuous sequence of events that results in a constriction between the embryo and the umbilical vesicle (yolk sac).
* As the head folds ventrally, part of the endodermal layer is incorporated into the developing embryonic head region as the foregut. Folding of the head region also results in the oropharyngeal membrane and heart being carried ventrally, and the developing brain becoming the most cranial part of the embryo.
* As the caudal eminence folds ventrally, part of the endodermal germ layer is incorporated into the caudal end of the embryo as the hindgut. The terminal part of the hindgut expands to form the cloaca. Folding of the caudal region also results in the cloacal membrane, allantois, and connecting stalk being carried to the ventral surface of the embryo.
* Folding of the embryo in the horizontal plane incorporates part of the endoderm into the embryo as the midgut.
* The umbilical vesicle remains attached to the midgut by a narrow omphaloenteric duct (yolk stalk). During folding of the embryo in the horizontal plane, the primordia of the lateral and ventral body walls are formed. As the amnion expands, it envelops the connecting stalk, omphaloenteric duct, and allantois, thereby forming an epithelial covering for the umbilical cord.
* The three germ layers differentiate into various tissues and organs so that by the end of the embryonic period, the beginnings of all the main organ systems have been established.
* The external appearance of the embryo is greatly affected by the formation of the brain, heart, liver, somites, limbs, ears, nose, and eyes. As these structures develop, the appearance of the embryo changes so that it has unquestionably human characteristics at the end of the eighth week.
* Because the beginnings of most essential external and internal structures are formed during the fourth to eighth weeks, this is the most critical period of development. Developmental disturbances during this period may give rise to major congenital anomalies of the embryo.
* Reasonable estimates of the age of embryos can be determined from the day of onset of the last normal menstrual period (LNMP), the estimated time of fertilization, ultrasound measurements of the chorionic sac and embryo, and examination of external characteristics of the embryo.

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