A lack of vitamin A on embryonic form of the major organ systems, the impact of construction
【Key Words】,,,,, vitamin
Influence of vitamin A deficiency on morphogenesis of main organ systems in embryo developing SONG Cui, LI Ting-yu
(Children's Hospital of Chongqing Medical University, Chongqing 400014, China)
Vitamin A (Vitamin A, VA) is a class derived from β
purple fragrant ketone derivatives, including retinol, retinaldehyde, retinoic acid and retinol esters. In which
retinoic acid (Retinoic acid, RA) is the most active derivative of VA. In normal embryonic development, the participation in the regulation of specific developmental events. As early as 30 years in the 19th century, there are studies show that in the embryonic development period,
pregnancy, maternal VA lacks (Vitamin A Deficiency, VAD) can affect the normal growth and development of offspring, or even result in offspring of various organs, the system congenital malformations. With the development of molecular biology and
the retinoic acid nuclear receptors in-depth study of people
from the gene level to the VA's role in embryonic development have a better understanding of [1,2]. This paper on the domestic and foreign scholars in recent years, the impact on
the VAD embryo form the major organ systems, and related mechanisms to build research are reviewed.
A retinoic acid nuclear receptors in embryonic development
Embryonic development in accordance with a certain space-
time model. VA derivatives of RA is essential for the normal development of embryos. VA primarily through two types of RA-
mediated retinoic acid nuclear receptors: RARs (retinoic acid receptors) and RXRs (retinoid X receptors), these two types of ligand-dependent transcription factor, regulating the
expression of target genes, thereby affecting the development of embryos. RARs and RXRs belong to the nuclear receptor
superfamily, have α, β, γ three kinds of subtypes, each
with subtypes encoded by different genes. Studies have found that retinoic acid nuclear receptor mutations in mice have occurred due to the abnormal and abnormal is very similar to
VAD, suggesting that VA on embryonic development of some of the effects produced by the nuclear retinoic acid receptor-
mediated achieved .
2 VA to the embryonic form of the major organ systems, the impact of construction
2.1 VA to build pattern in embryonic heart
The cardiovascular system is differentiated from the Sino-germ layers, first is the original formation of the cardiovascular system, on this basis, through growth, mergers, new, and shrinkage alterations gradual improvement process. VA
signal pathway in embryonic development has a very important role. Particular form of building in the heart of the process, the need to rely on RXR-α signaling pathway to regulate the
VA. RXR-α mutations can be induced myocardial thinning, or
even result in embryonic death. Merki et al , respectively epicardial and endocardial a series of tissue-specific RXR-α
mutation and found that RXR-α in mind the expression of
membrane form of construction for the normal heart is necessary. Also found that the performance of coronary artery anomalies-type and RXR-α deficiency related.
RA can occur related to the heart by regulating the expression of genes involved in embryonic form the heart of
building. The developing cardiovascular system express TbX1,
the genotype and phenotype of cardiac development are closely linked. Exogenous RA can not only cut TbX1, can also be through direct or indirect way to change the space TbX1 manifestations, which led to abnormal cardiac morphology, expressed as ventricular smaller outflow tract stenosis and atrial expanded, eventually caused an invalid loop or cycle termination of .
In addition to TbX1, the side plate mesoderm NKx2.5 and HAND1 key gene expression also affected by the regulation of
RA. Collop et al  will toad embryos observed after treatment with the RAR antagonist, in the heart of the formation of RA role in the process. Found in the heart of the early formation, RA can alter NKx2.5 and HAND1 expression, suggesting that side in the early mesoderm formation, at least to some extent by the regulation of RA. At the same time, the study found healing from the heart of the heart tube board needs to RA signals during boot. RA signals in mind only the healing of the heart tube plate in the process of a very
narrow time window to play a role, and its role in a dose-
dependent manner: high doses of RAR antagonist on both sides of myocardial wall can not be fusion; moderate doses of myocardial wall on both sides of blend, but the heart tube can
not form; low doses, the heart tube can be formed, but the heart of all of the partitions can not be completed. With the RA antagonist treatment, and their cardiac phenotype in the early stages of the formation of the performance of the heart similar to that of less mature myocardial cells. The above research suggests, RA signaling pathway through the RAR response element of the role took place during the formation for the toad heart is essential for the establishment of forms.
2.2 VA Morphology and Embryology of the nervous system to build
Nervous System originated in the neural ectoderm. Human embryonic 3rd weekend, the ectoderm ectodermal thickening between the notochord induce the formation of neural plate, neural plate formation of neural groove in central subsidence,
uplift of the edge of neural groove both sides of the neural crest. The formation of neural crest is the neural groove, the neural plate of columnar cells and normal cells in each ectodermal cell migration at cable .Neural crest in the
neural groove the middle of healing, the last before the formation of nerves in the first end of the hole and nerve holes. 4 weeks, complete closure of neural groove to neural tube. Human embryo the first 4 weeks, the first end of the
neural tube develop into the brain swelling, and the rest develop into the spinal cord. VA in the vertebrate embryo nervous system growth, differentiation, development and morphology has an important role in building .
Hindbrain during brain development is the transition
structure of the nervous system of the RA is the most sensitive region. White et al  found that VAD of the SD rats in pregnancy, 12.5d, embryonic development of the nervous system abnormalities appear visible to the naked eye, the most
obvious flaws in the hindbrain area, expressed as a large number of posterior cranial nerve (?, ?, ?, ? ) and the
posterior pharyngeal arch missing, foam ear swelling of ectopic and pre-primary vein. Shows the process of embryo formation need to participate in the tail of the hindbrain RA and related structures.
RA in different stages of embryonic development of the nervous system can play a role. Halilagic, etc.  to quail as a model study found that, in the early period of Corpus
Christi, VAD embryos the ventral neuroectodermal cell death increased, but the development of normal neural crest, to a later stage, the head mesenchymal and neural ectoderm ventral in a large number of apoptosis, the results of VAD embryos only reduced the formation of a single bulb and telencephalon between abnormal brain, and eventually died; in the early gastrulation, RA, including germ layers play a role in the development front, adjust the notochord the front surface of the endoderm to the neuroectodermal induction; in nerve-hole
closed when the RA involved in craniofacial morphology need to build signal transduction, including the amount of nasal prominence of interstitial formation and forebrain formation.
In recent years, the researchers set out to build form of
RA involved in the nervous system mechanism. Novitch et al  studies have shown that embryonic ventral spinal cord nerve cell apoptosis by the homology domain (home domain, HD) of regulation. Formed fibroblast growth factor (Fibroblast
Growth Factor, Fgfs) could inhibit the expression of HD proteins. The study found that Fgfs signal to escape the ventral spinal cord nerves can start to build the form. The type of vitamin A (Retinoid) can also be induced by spinal cord ventral nerve morphology build. Another study found that the tail of embryonic mesoderm arising from Fgfs inhibit neuronal differentiation, in neural differentiation and a reduced level of pre-Fgfs. The paraxial mesoderm of endogenous RA generated by down Fgfs, start to build neural
differentiation and neural patterns. Tips RA through the coordinating role and Fgfs embryonic body axis in the extended period, the promotion of neural differentiation [12,13]. Reposted elsewhere in the paper for free download http://
2.3 VA and embryo lung morphology Construction
Throat following respiratory differentiation comes from the foregut. In the embryonic stage of lung development, lung bud branches were accurate control. The embryos 6 to 17 months or so. RA in the lung bud branches process plays an important coordinating role. Chazaud, etc.  that, RAR-β is
currently the only involvement of the proximal airway to determine the formation of RAR transcripts. RA could be through the promotion of bronchus near the RAR-β gene
expression, inhibit the excessive lung bud branches, thus promoting the formation of proximal respiratory tract. The RAR antagonist BMS493 may be by inhibiting the expression of RAR-
β gene to promote the excessive lung bud branches, thus inhibiting the formation of proximal respiratory tract. On the other hand, RA synthase RALDH-1, form building regulator
Tgfb3, Foxa2, and cystic fibrosis transmembrane conductance regulator protein, Cftr were involved in the formation of the proximal airway. In vitro application of RA or BMS493 can
change the expression of the above-mentioned factors.
Surmised, RA can be raised to build regulator Tgfb3 shape and Foxa2, for the formation of the proximal airway to provide a stable environment that is conducive to the formation of the
Desai et al  The study found, RA selectively maintain foregut formation of regional lung mesodermal proliferation and induce Fgf10 expression, thereby contributing to lung bud branches. The RAR antagonist BMS493 may be by down-regulating
the expression of mesodermal Fgf10 selectively blocking the occurrence of lung bud branches. And further indicate that, while Fgf10 for foregut to differentiate into other organs, such as the thyroid gland, the pancreas is essential for
normal development, but the RA occurs only in the lung mesoderm regulate Fgf10 expression.
VA involved in embryonic lung function and its built form in the lungs and development, the formation of distal bronchial branches in the process of metabolism are closely
linked. Local regulation of RA signaling pathways for normal lung may be essential for the formation of branches. RALDH-2
enzymes involved in RA synthesis, while the RARE-lacZ is
produced RALDH-2 encoding genes. Both can increase RA
signaling pathway; P450RAI is the cytochrome P450 superfamily member, has the role of degradation of RA. COUPTF-? can
inhibit interstitial RARs, so that inactivation of RA target genes, thereby inhibiting RA signaling pathway proximal epithelium. In addition, COUPTF-? may also be inactivated by
RARE-lacZ to suppress RA signaling pathway. Therefore, P450RAI and COUPTF-? can be reduced RA signaling pathway; Fgf10 and Bmp4 in the distal bronchial expression during bud formation, Fgf10 expression in the inhibition by RA, while Fgf10
reduction can cause reduced Bmp4. Fgf10 and Bmp4 levels and changes in the distribution of bronchial buds may affect the form of a remote building. Malpel, etc.  The study found that in embryonic lung development, the formation of distal
bronchial branching process, RALDH-2, RARE-lacZ, P450RAI and
COUPTF-? signaling pathways co-regulate the activity of RA:
In the pulmonary form of early lung primordium office, RALDH-
2, RARE-lacZ expression was significantly, while the P450RAI, COUPTF-? no expression; With the progress of embryonic lung development, RALDH-2, RARE-lacZ expression gradually weakened, while the P450RAI, COUPTF-? level gradually higher, RA
signaling pathway showed a gradual decline from proximal to distal trend. RA signaling pathway in time and space on the
effective coordination, start Fgf10 and Bmp4 expression in a timely manner, so that the normal lung morphology to build.
2.4 VA and embryo morphology of other organ systems, to build
In recent years, studies have found that fully VAD quail embryos can not survive to the development of a limb, and knocked in addition RALDH-2 gene in mice does not appear limb bud, body shape abnormalities might be built later in the developing role of RA results; knock apart RALDH -2 genes in
mice also showed abnormal retinal development; in RAR compound mutant mice can be seen in genito-urinary system congenital
VA is the body's essential vitamins. It not only can affect the body after birth, growth and development is still embryonic form of participation in the various organ systems to build. Maternal nutritional status of VA can directly affect the fetus. VAD fetus during pregnancy the mother can reduce the level of VA, thus affecting the normal development of various tissues and organs, the formation of congenital malformations. So the VA for the pregnancy to ensure adequate maintenance of the health of pregnant women and newborns are very necessary.
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