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Morphogens, Embryonic Patterning and Axis Formation


Morphogens, embryonic patterning and axis formation overview

Embryos not only produce different types of cells (cell differentiation), but also the functional tissues and organs formed by these cells and form a stereoscopic pattern of ordered spatial structures. Embryonic cells form different tissues and organs, and the process of forming an ordered spatial structure becomes a pattern formation. In animal embryo development, the initial pattern formation mainly involved axis formation, somite formation, limb bud organ primordia and a series of related cell differentiation processes. The formation of axis is accomplished under a multi-level, network-controlled regulation of a series of genes.

Morphogens

The morphogen hypothesis: How do cells know that they have moved to the right place and should begin to participate in the formation of different tissues and organs? The morphogen hypothesis has been proposed to explain the morphogenesis behavior of cells in different parts of the embryo during development: Embryos are synthesized and secreted at specific parts of the embryo, and then spread to surrounding tissues to form a gradient of decreasing concentration. Cells can "perceive" the concentration of morphogens in their own parts through appropriate receptors, and the cells can estimate how far they are from the source of morphogen production and determine the direction of differentiation. In fact, the morphogen hypothesis emphasizes the influence of location information on morphogenesis. Scientists have affirmed the role of positional information in morphogenesis through studies of the development of chicken limb buds. During the development of an individual, the differentiation of cells in each tissue depends on its specific location information, which is set by the concentration gradient of the morphogen. As a classic model organism, Drosophila has been widely used in the study of morphogens. In the fruit fly system, Wg, Hh, and Dpp are the most typical and most widely studied three morphogen molecules. At present, there are many studies on their biological functions and their mechanisms of action at home and abroad. The results showed that the loss of HDAC1 function led to the up-regulation of the transcriptional target of the target gene ptc,ci and dpp, while the loss of HDAC3 resulted in the transcriptional up-regulation of Dpp target genesal, indicating that both HDAC1 and HDAC3 have histones deacetylase activity, but the function in regulating the transcription of the morphogen target gene is not identical. This may be due to two reasons: First, the localization of HDAC1 and HDAC3 in cells is not the same. HDAC1 is mainly present in the nucleus in Drosophila cells, and HDAC3 is present in both nucleus and cytoplasm. Therefore, the function of HDAC1 may be more focused on participating in certain biological processes in the nucleus (such as transcription), while HDAC3 may play more role in the cytoplasm; Second, HDAC1 and HDAC3 may be involved in the formation of different co-reactive transcriptional recombination complexes. As mentioned earlier, HDAC1 is mainly involved in the formation of the Sin3 complex, the Mi2/NuRD complex, and the CoREST complex, while HDAC3 is mainly involved in the formation of the SMRT/NCoR complex. These protein complexes are recruited to specific target genes by different sequence-specific DNA-binding proteins (such as transcription factors) to exert corresponding transcriptional regulation. The results showed that the loss of HDAC1 function led to the up-regulation of omb gene expression. But did not affect the expression of sal and vg. However, the loss of HDAC3 function led to up-regulation of Sal expression and down-regulation of Vg expression without affecting the expression of Omb. These results suggest that the regulation of gene transcription by HDAC1 and HDAC3 is not universal, but selective, which may be related to differences in the specific transcriptional mechanisms of each gene between the various signaling pathways and in the same pathway. For example, wg, hh and dpp downstream target gene transcription needs to activate different transcriptional regulatory factors (such as the activation of Wg downstream target gene requires Arm/ β-Catenin, Hh signaling pathway requires Ci/Gli), etc., and the mechanisms by which these transcription factors play a regulatory role are different, which makes them more dependent on the degree of histone acetylation. There are similar situations for different target genes under the same signaling pathway. For example, it is known that the transcription of Dpp downstream target genes sal,vg, andomb needs to work together with the transcription factor Mad and the transcriptional repressor Brk (Brinker), but they play a role in the transcription of each specific target gene. The way is different, especially whether the transcriptional activation of Obb depends on the direct binding of Mad to its transcriptional regulatory elements, which is still unclear. In addition, although Brk inhibits the transcription of Sal, Vg and Omb, the mechanism is not exactly the same. We found that loss of HDAC1 function led to upregulation of Omb, Ptc and Ci expression. Loss of HDAC3 function leads to increased transcription of Sal in Drosophila, but overexpression of HDAC1 or HDAC3 has no effect on the expression of downstream target genes. A possible explanation is that inhibition of transcription of these genes by HDAC1 or HDAC3 requires synergistic effects of other limiting cofactors. Overexpression of HDAC1 or HDAC3 alone is not enough to produce effects. For example, transcriptional inhibition of Sal, Vg and Omb requires Brk involvement.

Embryonic Patterning

Human fertilization is done in the upper segment of the fallopian tube. Embryonic development begins when the fertilized egg is in the middle of the fallopian tube. The fertilized egg undergoes cleavage while descending along the fallopian tube toward the uterus and reaches the uterus in 2 to 3 days. The embryo at that time was a hollow small sphere composed of many cells called a blastocyst. About a week after fertilization, the blastocyst is implanted into the thickened intrauterine strand, which is called pregnancy. The blastocyst grows up through cell division and cell differentiation and is divided into two parts. One part is that the embryo itself will develop into a fetus in the future; the other part will evolve into the outer membrane of the embryo, the most important being the amnion, placenta and umbilical cord, and the fetus exchanges material through the placenta and the mother. In the first two months, the embryo continues to divide and differentiate cells, produce various cells, and form various tissues and organs. This is a period of development and sensitivity, and it has poor resistance and adaptability to various external stimuli. To pay great attention to safety, including pregnant women taking drugs, receiving radiation or exposure to other harmful factors, will affect the normal development of the fetus; by the end of the third month, the various organ systems have been basically completed, known as the fetus. Direct development and indirect development, as two models, can summarize the embryonic development of all multicellular animals, but not enough to express the characteristics of the embryonic development of invertebrates and their interconnection. The late embryonic development of the invertebrates and the morphogenesis of the metamorphosis period have their own development directions, and it is, of course, difficult to generalize them into a few models. However, if the early embryonic development process is prevailing, there will be some commonality or regularity in morphogenesis, whether between similar levels of evolution or between different levels of evolution. This aspect not only reflects the mutual restraint relationship between individual development and phylogeny but also reflects the level of evolution and the closeness of kinship. Since the 1940s, the above content has become an important basis for determining the location of each invertebrate and explaining its evolutionary direction. Therefore, it is also need establish the theoretical basis for establishing the basic model of invertebrate embryo development.

Axis formation

Nowadays, the most research on axis formation is the formation of axis of Drosophila and vertebrates. The formation of axis is completed under the multi-level and network control of a series of genes. The axis refers to the anterior-posterior axis and the dorsal-ventral axis of the embryo. In the initial development of Drosophila, a positional information network constructed by the maternal effect gene activates the expression of zygotic genes and controls the construction of the Drosophila somatic pattern. There are serval very important morphogens, BCD and HB, for regulating the formation of the anterior-posterior axis of embryos. The zygote genes are first regulated, and the protein product primers of different concentrations of zygote genes cause the expression of paired control genes, expression bands perpendicular to the front and rear axles. The paired control gene protein product activates transcription of the somite polarity gene, further dividing the embryo into 14 individual segments. Gap genes, paired genes, and somatic polarity genes together regulate the expression of homeotic genes and determine the developmental fate of each segment. Among the four maternal effector genes involved in the formation of Drosophila axis, the dorsal-abdominal system is the most complex, and the gametes distributed on the ventral warm yellow membrane are activated by gametes localized on the ventral warm yellow membrane of the egg, regulating the zygote gene. Expression of the zygote target gene by the dorsal-ventral system, the dorsoventral system regulates the zygote target genes in a similar manner to the front-end system and is accomplished by a transcription factor concentration gradient. The vertebrate axis formation is related to the action of the protein-maternal determinant encoded by the maternal effector gene and the interaction between cells and the function of a series of signal transduction pathway molecules. Amphibian embryonic axis are regulated by the nieuwkoop center and organizers. The embryonic shield of fish is a homolog of the amphibian back lip and has a similar regulatory effect. The regulation of birds and mammals is related to the formation of primitive strips.

Reference

  1. Ulloa F, Briscoe J. Morphogens and the control of cell proliferation and patterning in the spinal cord. Cell Cycle. 2007, 6(21):2640-2649.
  2. Simpsonbrose M, Treisman J, Desplan C. Synergy between the hunchback and bicoid morphogens is required for anterior patterning in Drosophila. Cell. 1994, 78(5):855-865.
  3. Dubrulle J, Pourquié O. Coupling segmentation to axis formation. Development. 2004, 131(23):5783-93.
  4. Kenney N J, Adkins H B, Sanicola M. Nodal and Cripto-1: embryonic pattern formation genes involved in mammary gland development and tumorigenesis. Journal of Mammary Gland Biology & Neoplasia. 2004, 9(2):133-44.
  5. Solnica-Krezel L, Driever W. The role of the homeodomain protein Bozozok in zebrafish axis formation. International Journal of Developmental Biology. 2001, 45(1):299-310.

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